Methods and systems for assessment of clinical infertility

ABSTRACT

Methods and computer-based systems for facilitating assessment of clinical infertility are provided. The methods and systems can be implemented to, for example, facilitate assessment of a subject for an in vitro fertilization treatment cycle, including determining probability of a live birth event. The methods and systems can be implemented to, for example, facilitate a determination of success implantation of embryos, selection of an optimal number of embryos to transfer, and determination of success in subsequent in vitro fertilization treatment cycles following an unsuccessful treatment cycle.

CROSS-REFERENCE

This application claims the benefit of U.S. Provisional Application Nos. 61/077,439, filed Jul. 1, 2008, and 61/081,596, filed Jul. 17, 2008, which applications are incorporated by reference herein in their entirety.

GOVERNMENT RIGHTS

This invention was made with government support under federal grant nos. R01 GM067250 and R01 HD057970 awarded by the National Institutes of Health. The United States Government has certain rights in this invention.

BACKGROUND OF THE INVENTION

Reproductive failure is a serious problem that has been addressed clinically by various assisted reproductive technologies, including in vitro fertilization (IVF) and embryo transfer (ET). These procedures might be expected to yield exceptionally high conception rates as in vitro fertilization provides embryos that appear normal at a morphological level for transfer into a fully primed recipient. Despite these efforts the success rate of IVF/ET is less than ideal. In the published data for IVF/ET in the United States and Canada in 1994, there were 26,961 initiated cycles of standard IVF. Of these, 86.2% led to retrieval and of these 90.2% led to a transfer. However, the overall success rate in terms of clinical pregnancies was 22.7% per initiated cycle and a 29.1% pregnancy rate per transfer.

Additionally, there appears to be a high incidence of early pregnancy loss after in vitro fertilization with a biochemical pregnancy rate of 18% and a spontaneous abortion rate of 27%. Thus, it appears that the IVF technique has been well optimized but implantation failure may be the cause for a large number of losses with ET and this peri-implantational loss is an area of potential improvement. A major factor in the success rate of various assisted reproductive technologies is endometrial receptivity, a transient state that must be coordinated with embryo development to implantation-competent blastocysts.

IVF is an expensive procedure and can be psychologically traumatic for a patient. Surgical procedures are required to collect eggs from a female for IVF and, following fertilization, further surgery is required to implant the fertilized eggs in the womb. The recipient must then wait for a period of time before it can be determined whether or not pregnancy has been established. In some cases, pregnancy may never be achieved despite repeated attempts, and these cases can represent a considerable expense to the patient and society, both in financial and human terms.

Therefore, until success rates of IVF can be improved, it would be desirable to be able to identify recipients for whom IVF is unlikely to be successful prior to treatment, so that such patients may avoid the above mentioned costs and trauma of the IVF procedure.

The present invention addresses these needs.

SUMMARY OF THE INVENTION

Methods and computer-based systems for facilitating assessment of clinical infertility are provided. The methods and systems can be implemented to, for example, facilitate assessment of a subject for an in vitro fertilization treatment cycle, including determining probability of a live birth event. The methods and systems can be implemented to, for example, facilitate a determination of success of implantation of embryos, selection of an optimal number of embryos to transfer, and determination of success in subsequent in vitro fertilization treatment cycles following an unsuccessful treatment cycle.

These and other objects, advantages, and features of the invention will become apparent to those persons skilled in the art upon reading the details of the invention as more fully described below.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is best understood from the following detailed description when read in conjunction with the accompanying drawings. It is emphasized that, according to common practice, the various features of the drawings are not to-scale. On the contrary, the dimensions of the various features are arbitrarily expanded or reduced for clarity. Included in the drawings are the following figures.

FIG. 1 shows the source of the data. Panel A shows the IVF cycles performed in 2005. Panel B shows the utilization of oocytes and embryos in 665 fresh, non-donor IVF cycles. All numbers in Panel A indicate the number of cycles and numbers in Panel B indicate the number of oocytes or embryos. Fresh cycles are defined by ovarian stimulation of gonadotropins and embryo transfer performed within the same cycle; cryopreserved cycles utilize embryos that were obtained and cryopreserved from a previous cycle; “freeze-all” are cycles in which ovarian stimulation was performed, but embryos were cryopreserved instead of being transferred back within the same cycle for medical or non-medical reasons. 157 cycles were removed from analysis for a variety of medical and non-medical reasons that did not result in fresh embryo transfer.

FIG. 2 shows the distribution of all embryos from 665 fresh, non-donor IVF cases according to their cell number on Day 3.

FIG. 3 shows variables and their relative importance in determining A) number of 8-cell embryos (Panel A), day 3 FSH (Panel B), and the total number of embryos (Panel C).

FIG. 4 shows that translational block of cyclin A2 by Ccna2-MO causes embryos to arrest at the 2-cell stage. Panel A shows Ccna2 expression in 1- to 2-cell embryos by RT-PCR. Panel B shows nuclear cyclin A2 localization was absent in 83.4±6.0% of Ccna2-MO-injected embryos but present in all uninjected embryos; p<0.01). Panel C shows that ˜50 kD cyclin A2 protein was not detected in Ccna2-MO-injected embryos.

FIG. 5, panel A shows that Ccna2-MO induced higher rates of 2-cell stage arrest compared to controls (p<0.01). Panel B shows that only 1.8±1.8% of Ccna2-MO-injected embryos reached blastocyst stage (p=0.06 compared to Ccna2-MM). Panel C shows that the rates of 2-cell stage arrest decreased with the concentration of Ccna2-MO (p=0.05 for 0.5 mM; p=0.01 for 0.25 mM). Panel D shows that the rate of blastocyst development at were higher at 0.25 mM than at 0.75 mM (p<0.001). All columns and error bars represent mean±s.e.m., respectively, from at least three independent sets of experiments. Scale bar 40 μm. See Table 1 for the targeted sequence of all MOs used, and Table 7 for the total number of embryos tested in each set of experiments.

FIG. 6 shows the mechanisms that regulate mammalian embryo development at the earliest stages. In wild type (+/−) embryos, maternal transcripts are present before embryonic genome activation (EGA), while maternal and embryonic transcripts are present at maternal-embryonic transition stage, both resulting in production of a normal gene product (Panel A). In homozygous null mutant (−/−) embryos generated from a mother that is heterozygous (+/−) for the null mutation, persistent maternal transcripts and/or proteins may “rescue” or delay the phenotype onset (Panel B). In contrast, homozygous null mutant embryos generated from a homozygous mutant female, or a female with oocyte-specific gene deletion, the observed defects may reflect oocyte defects, rather than specific gene requirement in the early embryo (Panel C). Therefore, these strategies do not address the precise roles of specific genes at the cusp of EGA or during EGA, when both maternal and early embryonic transcripts may be present simultaneously. Cytoplasmic microinjection of antisense morpholino oligonucleotides (MOs) into wild type embryo just at or before EGA results in specific translational block of both maternal and embryonic gene transcripts (Panel D). Since MOs persist for at least a few cycles of cell division, gene-specific translational block is presumably effective until the morula-blastocyst stages. The absence of gene product during these developmental stages would reveal critical gene function and unmask early phenotypes that may not be detectable in conventional gene-targeting strategies by homologous recombination and transgenesis. While this model is well established in other species, it shifts the paradigm from investigating function of embryonic genes to that of gene products regardless of their maternal or embryonic origin.

FIG. 7 shows the experimental strategy. Embryos at the 2 pronuclei (2PN) or 1-cell stage were collected from wild type matings, and injected with an antisense morpholino oligomer (MO) that was designed to target a specific gene. MO binds to 5′ UTR or transcription start site and blocks translation by steric hindrance. Microinjected embryos and uninjected control embryos were cultured in vitro and observed for developmental phenotypes such as fragmentation, or arrest at the 2-cell, 4-cell, multicell, or morula stages. If a gene-specific MO produces the same phenotype consistently, while the mismatch control MO allows normal development, then knockdown of the gene of interest was validated by immunocytochemistry and/or immunoblotting. Mechanism of gene function was further investigated by obtaining global gene expression profiles from injected and control embryos at the mid-2-cell stage (43 hours post-HCG). Candidate downstream genes were tested for differential expression, and gene function in the early embryo.

FIG. 8 shows Oct4 expression in mouse zygote by single embryo RT-PCR.

FIG. 9 shows that Oct4 is required for early embryo development prior to formation of the blastocyst. Panel A shows that Oct4-MO-injected embryos arrested at multicell stage, while controls reached blastocyst stage. Panel B shows that Oct4 knockdown induced higher arrest rates at the 1- to multicell stages; p<0.01. Panel C shows that None of the Oct4-MO-injected embryos developed to blastocysts. Panel D shows that the rates of arrest at the 1- to multicell stages decreased with concentration of Oct4-MO (p<0.01). Panel E shows that there was a non-significant trend for higher rates of blastocyst development with decreasing concentrations of Oct4-MO.

FIG. 10 shows that decreased Oct4 expression was evident by the 4-cell stage in Oct4-MO-injected embryos. Oct4 signal was absent in embryos injected with Oct4-MO, but its nuclear localization was present in uninjected and mismatch controls. Scale bar 40 μm.

FIG. 11, Panel A, shows that nuclear Oct4 expression is absent in Oct4-MO-injected embryos (top panel) but present in Oct4-MM-injected embryos and uninjected. Panel B shows that compared to no coinjection or mEYFP mRNA coinjection, coinjection of 36 or 3.6 ng/μL of Oct4 mRNA resulted in partial rescue of the Oct4-MO-induced phenotype by specifically decreasing the arrest rates at the 1- to multicell stages, which resulted in higher rates blastocyst development (p<0.01). Panel C shows that overexpression of Oct4 mRNA induced higher developmental arrest in a dose-dependent manner, such that blastocyst rates are significantly lower after injection of Oct4 mRNA at 36 or 90 ng/μL, compared to overexpression of mEYFP (p<0.01). Gene overexpression was validated by q-PCR or immunocytochemistry (data not shown). (Scale bar=40 μm).

FIG. 12 shows decreased Oct4 expression at the multicell stage in Oct4-MO-injected embryos. Only 6.4±3.2% of Oct4-MO-injected embryos showed nuclear Oct4 signal, while 88.9±11.1% of Oct4-MM-injected embryos and 82.7±10.9% of uninjected control embryos showed unequivocal nuclear Oct4 expression at the multicell stage; p<0.05.

FIG. 13 shows confirmation of the requirement of Oct4 in early embryo development by Oct4E4-MO, an antisense morpholino that targets the splice site of exon 4 of Oct4. Panel A shows sites targeted by the two morpholinos, Oct4-MO and Oct4E4-MO. Oct4-MO targets the 25 nucleotides starting at the ATG start site, while Oct4E4-MO targets the splice site at the intron (I)-exon (E) boundary of the 4^(th) exon (E4). Removal of E4 is expected to result in a protein product that lacks the DNA-binding and activation domains. Panel B shows that 64.6±19.9% of embryos injected with Oct4E4-MO, while none that were injected with the mismatch control, Oct4E4-MM, arrested at the 2-cell stage. Panel C shows that blastocyst development is severely compromised after injection of Oct4E4-MO compared to the mismatch control, Oct4E4-MM.

FIGS. 14 and 15 show gene regulation by Oct4. FIG. 14, Panel A shows unsupervised clustering of 3 Oct4 knockdown, 3 Ccna2 knockdown, and 6 uninjected (NI) pooled embryo samples, and increased (red) and decreased (blue) gene expression. Scale is standard deviation FIG. 14, Panel B shows intersection of differentially expressed genes in Oct4 and Ccna2 knockdown embryos. FIG. 14, Panel C and FIG. 15 show relative expression of Oct4 knockdown by single-embryo q-PCR for FIG. 14, Panel C overexpressed genes (p<0.05 for Hes5) and FIG. 15 downregulated genes (*p<<0.001, **p<0.05, ***p<0.1). TR translational repression. Error bars indicate s.e.m.

FIG. 16 shows models of Oct4 function at the 1- to 2-cell stage. Panel A shows genes whose Absolute (ΔC_(T)) (red) is greater than its s.e.m. (blue), are ordered clockwise based on increasing s.e.m. (Log scale.) Panel B shows proposed regulation of various modules by Oct4 via transcriptional and post-transcriptional mechanisms.

FIG. 17 shows a summary of the data source for the live birth analysis. The numbers in the boxes indicate the number of fresh cycles performed in the Stanford IVF center through 2003-06. The cycles that were not included were related to: gestational carriers, Cryo. ET or cryopreserved embryo transfer (cycles which utilized frozen embryos, irrespective of whether the cycle was performed at Stanford or outside), donor oocytes (non-self oocytes), recipient cycles and cycles in which no gonadotropin was injected. 9 cycles were excluded from analysis for duplicated entries and unknown outcomes. The cycles analyzed were further classified into Cycles 1, 2, 3 or beyond, depending on the number of times the patient returned for a fresh IVF cycle.

FIG. 18 shows a summary of live birth outcomes. Different boxes represented C1 (first-IVF cycle), C2 (second-IVF cycle), and C3 (third-IVF cycle). Each box shows the number of cycles with live birth (LB+) or no live birth (LB−) outcomes, the percentage of the total number (N) of cycles analyzed and the number of patients that dropped out and did not return.

FIG. 19 is a graph showing distribution of embryos with respect to developmental stage. The distribution of 2969 fresh, non-donor IVF cases from all three cycles according to their cell number on day 3 of in vitro culture. The number of cells per embryo and the maximum number of embryos (−40%) that had 8 cells were similar amongst cycles C1 (no fill pattern), C2 (horizontal fill pattern), and C3 (vertical fill pattern).

FIG. 20 shows prediction models and their temporal relationship with a typical IVF cycle. An IVF cycle comprises of down-regulation of endogenous gonadotropins and the menstrual cycle using oral contraceptive pill (OCP), periodic FSH injections and cycle monitoring by ultrasound with or without serum estradiol, followed by hCG injection to simulate endogenous LH surge, oocyte retrieval, fertilization by IVF or ICSI, in vitro embryo culture, embryo transfer, and cryopreservation of excess embryos. The three black stars represent the points at which patients can take an informed decision about further treatment options and whether to continue treatment. The Pre-IVF model extends until the treatment start date. The Pre-OR (oocyte retrieval) model extends until the hCG injection. The Post-IVF model includes all variables until embryo transfer.

FIGS. 21A, 21B, and 21C show tree models for three analysis groups: Pre-IVF (21A), Pre-OR (21B) and Post-IVF (21C). The pie-charts show the percentage of live births (LB) among the total number (N) of cycles analyzed. Terminal populations are labeled as population 1 (Pop 1), etc., with its live birth rate indicated.

FIG. 22 shows inclusion and exclusion criteria for 2007 data set.

FIG. 23 shows that Pre-IVF, Pre-OR and Post-IVF models identify distinct populations with differential live birth rates.

FIGS. 24A, 24B, and 24C show comparison of live birth rates between Pre-IVF (FIG. 23A), Pre-OR- (FIG. 23 B), Post-IVF models and an age-based control model.

FIG. 25 shows that Post-IVF model C1 population assignment predicts differential live birth rates in C2 and cumulative live birth rates in subsequent cycles (C2 and C3).

FIG. 26 shows results of gene chip experiments performed at the 1-cell stage.

FIG. 27 shows results of gene chip experiments performed at the 4-cell stage.

FIG. 28 shows results of gene chip experiments performed at the 8-cell stage.

FIG. 29 shows a correlation of two gene chip experiments showing expression of a panel of genes at various cell stages.

FIG. 30 shows a correlation of two gene chip experiments showing expression of a panel of genes at various cell stages.

Before the present embodiments are described, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. It is understood that the present disclosure supercedes any disclosure of an incorporated publication to the extent there is a contradiction.

It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and reference to “the compound” includes reference to one or more compounds and equivalents thereof known to those skilled in the art, and so forth.

It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely”, “only” and the like in connection with the recitation of claim elements, or the use of a “negative” limitation.

The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

DEFINITIONS

The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a mammal being assessed for treatment and/or being treated. In an embodiment, the mammal is a human, such as a female human. The terms “subject,” “individual,” and “patient” thus encompass individuals in need of assessment of clinical infertility, including those who have undergone or are candidates for an in vitro fertilization cycle.

As used herein, the term “correlates,” or “correlates with,” and like terms, refers to a statistical association between instances of two events, where events include numbers, data sets, and the like. For example, when the events involve numbers, a positive correlation (also referred to herein as a “direct correlation”) means that as one increases, the other increases as well. A negative correlation (also referred to herein as an “inverse correlation”) means that as one increases, the other decreases.

A “biological sample” encompasses a variety of sample types obtained from an individual. The definition encompasses blood and other liquid samples of biological origin, solid tissue samples such as a biopsy specimen or tissue cultures or cells derived therefrom and the progeny thereof. The definition also includes samples that have been manipulated in any way after their procurement, such as by treatment with reagents; washed; or enrichment for certain cell populations, such as cancer cells. The definition also includes sample that have been enriched for particular types of molecules, e.g., nucleic acids, polypeptides, etc. The term “biological sample” encompasses a clinical sample, and also includes tissue obtained by surgical resection, tissue obtained by biopsy, cells in culture, cell supernatants, cell lysates, tissue samples, organs, bone marrow, blood, plasma, serum, and the like. A “biological sample” includes a sample obtained from a patient's uterus, including embryo cultures.

The terms “gene product” and “expression product” are used interchangeably herein in reference to a gene, to refer to the RNA transcription products (transcripts) of the gene, including mRNA and the polypeptide translation products of such RNA transcripts, whether such product is modified post-translationally or not. The terms “gene product” and “expression product” are used interchangeably herein, in reference to an RNA, particularly an mRNA, to refer to the polypeptide translation products of such RNA, whether such product is modified post-translationally or not. A gene product can be, for example, an unspliced RNA, an mRNA, a splice variant mRNA, a polypeptide, a post-translationally modified polypeptide, a splice variant polypeptide, etc.

As used herein, the term “normalized expression level” refers to an expression level of a response indicator gene relative to the level of an expression product of a reference gene(s).

As used herein, the terms “label” and “detectable label” refer to a molecule capable of being detected, where such molecules include, but are not limited to, radioactive isotopes, fluorescers (fluorophores), chemiluminescers, chromophores, enzymes, enzyme substrates, enzyme cofactors, enzyme inhibitors, chromophores, dyes, metal ions, metal sols, ligands (e.g., biotin, avidin, strepavidin or haptens), intercalating dyes and the like. The term “fluorescer” or “fluorophore” refers to a substance or a portion thereof which is capable of exhibiting fluorescence in a detectable range.

As used herein, the term “target nucleic acid region” or “target nucleic acid” refers to a nucleic acid with a “target sequence” to be detected (e.g., in a method involving nucleic acid hybridization and/or amplification). The target nucleic acid may be either single-stranded or double-stranded and may or may not include other sequences besides the target sequence (e.g., the target nucleic acid may or may not include nucleic acid sequences upstream or 5′ flanking sequence, and may or may not include downstream or 3′ flanking sequence. Where detection is by amplification, these other sequences in addition to the target sequence may or may not be amplified with the target sequence.

The term “primer” or “oligonucleotide primer” as used herein, refers to an oligonucleotide which acts to initiate synthesis of a complementary nucleic acid strand when placed under conditions in which synthesis of a primer extension product is induced, e.g., in the presence of nucleotides and a polymerization-inducing agent such as a DNA or RNA polymerase and at suitable temperature, pH, metal ion concentration, and salt concentration. Primers are generally of a length compatible with their use in synthesis of primer extension products, and can be in the range of between about 8 nucleotides and about 100 nucleotides (nt) in length, such as about 10 nt to about 75 nt, about 15 nt to about 60 nt, about 15 nt to about 40 nt, about 18 nt to about 30 nt, about 20 nt to about 40 nt, about 21 nt to about 50 nt, about 22 nt to about 45 nt, about 25 nt to about 40 nt, and so on, e.g., in the range of between about 18 nt and about 40 nt, between about 20 nt and about 35 nt, between about 21 and about 30 nt in length, inclusive, and any length between the stated ranges. Primers can be in the range of between about 10-50 nucleotides long, such as about 15-45, about 18-40, about 20-30, about 21-25 nt and so on, and any length between the stated ranges. In some embodiments, the primers are not more than about 10, 12, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, or 70 nucleotides in length. In this context, the term “about” may be construed to mean 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 more nucleotides either 5′ or 3′ from either termini or from both termini.

Primers are in many embodiments single-stranded for maximum efficiency in amplification, but may alternatively be double-stranded. If double-stranded, the primer is in many embodiments first treated to separate its strands before being used to prepare extension products. This denaturation step is typically effected by heat, but may alternatively be carried out using alkali, followed by neutralization. Thus, a “primer” is complementary to a template, and complexes by hydrogen bonding or hybridization with the template to give a primer/template complex for initiation of synthesis by a polymerase, which is extended by the covalent addition of bases at its 3′ end.

A “primer pair” as used herein refers to first and second primers having nucleic acid sequence suitable for nucleic acid-based amplification of a target nucleic acid. Such primer pairs generally include a first primer having a sequence that is the same or similar to that of a first portion of a target nucleic acid, and a second primer having a sequence that is complementary to a second portion of a target nucleic acid to provide for amplification of the target nucleic acid or a fragment thereof. Reference to “first” and “second” primers herein is arbitrary, unless specifically indicated otherwise. For example, the first primer can be designed as a “forward primer” (which initiates nucleic acid synthesis from a 5′ end of the target nucleic acid) or as a “reverse primer” (which initiates nucleic acid synthesis from a 5′ end of the extension product produced from synthesis initiated from the forward primer). Likewise, the second primer can be designed as a forward primer or a reverse primer.

As used herein, the term “probe” or “oligonucleotide probe”, used interchangeable herein, refers to a structure comprised of a polynucleotide, as defined above, which contains a nucleic acid sequence complementary to a nucleic acid sequence present in the target nucleic acid analyte (e.g., a nucleic acid amplification product). The polynucleotide regions of probes may be composed of DNA, and/or RNA, and/or synthetic nucleotide analogs. Probes are generally of a length compatible with their use in specific detection of all or a portion of a target sequence of a target nucleic acid, and are in many embodiments in the range of between about 8 nt and about 100 nt in length, such as about 8 to about 75 nt, about 10 to about 74 nt, about 12 to about 72 nt, about 15 to about 60 nt, about 15 to about 40 nt, about 18 to about 30 nt, about 20 to about 40 nt, about 21 to about 50 nt, about 22 to about 45 nt, about 25 to about 40 nt in length, and so on, e.g., in the range of between about 18-40 nt, about 20-35 nt, or about 21-30 nt in length, and any length between the stated ranges. In some embodiments, a probe is in the range of between about 10-50 nucleotides long, such as about 15-45, about 18-40, about 20-30, about 21-28, about 22-25 and so on, and any length between the stated ranges. In some embodiments, the primers are not more than about 10, 12, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, or 70 nucleotides in length. In this context, the term “about” may be construed to mean 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 more nucleotides either 5′ or 3′ from either termini or from both termini.

Where a nucleic acid is said to hybridize to a recited nucleic acid sequence, hybridization is under stringent conditions. An example of stringent hybridization conditions is hybridization at 50° C. or higher and 0.1×SSC (15 mM sodium chloride/1.5 mM sodium citrate). Another example of stringent hybridization conditions is overnight incubation at 42° C. in a solution: 50% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 μg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in 0.1×SSC at about 65° C. Stringent hybridization conditions are hybridization conditions that are at least as stringent as the above representative conditions, where conditions are considered to be at least as stringent if they are at least about 80% as stringent, e.g., at least about 90% as stringent as the above specific stringent conditions.

DETAILED DESCRIPTION OF THE INVENTION

As noted above, methods and computer-based systems for facilitating assessment of clinical infertility are provided. The methods and systems can be implemented to, for example, facilitate assessment of a subject for an in vitro fertilization treatment cycle. The methods and systems can be implemented to, for example, facilitate a determination of success for implantation of embryos, selection of an optimal number of embryos to transfer, and determination of success in subsequent in vitro fertilization treatment cycles following an unsuccessful treatment cycle.

In certain embodiments, the method includes obtaining items of information from a female subject to provide a profile for the female subject, wherein each item of information relate to preselected patient variables, comparing the profile for the female subject to a library of known profile patterns known to be indicative of responsiveness to an in vitro fertilization procedure using an algorithm based upon the preselected patient variables, wherein the comparing provides an evaluation of the female subject for an in vitro fertilization procedure. In certain embodiments, the in vitro fertilization procedure is at least a second vitro fertilization procedure for said female subject.

The items of information may be provided by the female subject based on a written or electronic questionnaire or may be requested, transcribed, or otherwise logged, by a health care practitioner, such as a doctor, nurse, technician, or the like, during or concurrent with a medical evaluation that may optionally be associated with a determination to undergo a first or subsequent in vitro fertilization cycle.

Exemplary items of information relating to preselected patient variables include, but are not limited to: patient characteristics, such as age, previous infertility history, clinical diagnosis; clinical treatment information, such as type of medication, number of days of stimulation, number of oocytes, etc.; conventional embryo morphology data, such as number of embryos, developmental stage, grade, and the like. In some embodiments, the information includes age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, and number of 8-cell embryos transferred.

In certain embodiments, the in vitro fertilization procedure provides for a live birth event following the in vitro fertilization procedure. In such embodiments, the method provides a probability of a live birth event occurring resulting from the first or subsequent in vitro fertilization cycle based at least in part on items of information from the female subjects.

In some embodiments, the female subject is a pre-in vitro fertilization (pre-IVF) procedure patient. In certain embodiments, the items of information relating to preselected patient variables for determining the probability of a live birth event for a pre-IVF procedure patient may include age, diminished ovarian reserve, 3 follicle stimulating hormone (FSH) level, body mass index, polycystic ovarian disease, season, unexplained female infertility, number of spontaneous miscarriages, year, other causes of female infertility, number of previous pregnancies, number of previous term deliveries, endometriosis, tubal disease, tubal ligation, male infertility, uterine fibroids, hydrosalpinx, and male infertility causes.

In some embodiments, the female subject is a pre-surgical (pre-OR) procedure patient (pre-OR is also referred to herein as pre-oocyte retrieval). In certain embodiments, the items of information relating to preselected patient variables for determining the probability of a live birth event for a pre-OR procedure patient may include age, endometrial thickness, total number of oocytes, total amount of gonatropins administered, number of total motile sperm after wash, number of total motile sperm before wash, day 3 follicle stimulating hormone (FSH) level, body mass index, sperm collection, age of spouse, season number of spontaneous miscarriages, unexplained female infertility, number of previous term deliveries, year, number of previous pregnancies, other causes of female infertility, endometriosis, male infertility, tubal ligation, polycystic ovarian disease, tubal disease, sperm from donor, hydrosalpinx, uterine fibroids, and male infertility causes.

In some embodiments, the female subject is a post-in vitro fertilization (post-IVF) procedure patient. In certain embodiments, the items of information relating to preselected patient variables for determining the probability of a live birth event for a post-IVF procedure patient may include blastocyst development rate, total number of embryos, total amount of gonatropins administered, endometrial thickness, flare protocol, average number of cells per embryo, type of catheter used, percentage of 8-cell embryos transferred, day 3 follicle stimulating hormone (FSH) level, body mass index, number of motile sperm before wash, number of motile sperm after wash, average grade of embryos, day of embryo transfer, season, number of spontaneous miscarriages, number of previous term deliveries, oral contraceptive pills, sperm collection, percent of unfertilized eggs, number of embryos arrested at 4-cell stage, compaction on day 3 after transfer, percent of normal fertilization, percent of abnormally fertilized eggs, percent of normal and mature oocytes, number of previous pregnancies, year, polycystic ovarian disease, unexplained female infertility, tubal disease, male infertility only, male infertility causes, endometriosis, other causes of female infertility, uterine fibroids, tubal ligation, sperm from donor, hydrosalpinx, performance of ICSI, or assisted hatching.

Additional examples of parameters are provided in the examples section, including, for example, Tables 13 and 15.

In certain embodiments, the method includes obtaining items of information relating to at least two preselected patient variables, or more. As such, in other embodiments, the method includes obtaining items of information relating to at 3 or more preselected patient variables, including 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 12 or more, 15 or more, 17 or more, 20 or more, and the like.

In certain embodiments, the method includes assigning a weighted relative importance to each preselected patient variable in relation to other preselected patient variables. For example, in an analysis of a Pre-IVF model subject, the preselected patient variables of age and diminished ovarian reserve are given a higher relative importance value over other preselected patient variables, such as, for example, body mass index, tubular disease, and endometriosis. In such embodiments, the sum of the relative importance of each preselected patient variables will equal 100.

In another embodiment, in an analysis of a Pre-OR model subject, the preselected patient variables of total amount of gonoatropins, endometrial thickness and age are given a higher relative importance value over other preselected patient variables, such as, for example, number of previous pregnancies, tubal ligation and number of spontaneous miscarriages. In such embodiments, the sum of the relative importance of each preselected patient variables will equal 100.

In yet another embodiment, in an analysis of a Post-IVF model subject, the preselected patient variables of blastocyst development rate, total number of embryos, total amount of gonatropins administered, and endometrial thickness are given a higher relative importance value over other preselected patient variables, such as, for example, body mass index, number of motile sperm before wash, number of motile sperm after wash, average grade of embryos, and day of embryo transfer. In such embodiments, the sum of the relative importance of each preselected patient variables will equal 100.

In some embodiments, the comparing includes applying a decision rule. In some embodiments, the data analysis algorithm comprises the use of a classification tree. In other embodiments, the data analysis algorithm is nonparametric, such as using a Wilcoxon Signed Rank Test. In certain embodiments, the data analysis algorithm detects differences in a distribution of feature values. In some embodiments, the data analysis algorithm includes using a multiple additive regression tree. In some embodiments, the data analysis algorithm is a logistic regression.

In further embodiments, the method includes assessment of a gene expression profile of an arrested embryo from the female subject. For example, embryos that have arrested, for example embryos that have fewer than about 5 cells on day 3 following in vitro fertilization, are tested for a relative expression level of a panel of genes that are critical to embryo development. The gene expression profile is then compared to a control gene expression profile.

Any gene that for which normalized expression level is correlated (either positively or negatively) with infertility or likelihood of success or failure of an in vitro fertilization cycle is suitable for use with the methods of the invention. Exemplary genes include, but are not limited to, Oct4, Eif3c, Papola, Piwil2, Eif3b, Eif4b, Rbm3, Cpsf4 and other genes found to be down- or upregulated upon Oct4 knockdown, or the knockdown of another gene encoding a pluripotency regulator (e.g. Sal14). Other exemplary genes include those listed in Tables 8A, 8B, 9A, and 9B in attached Appendixes A-D, as well as Table 12. These gene products are referred to herein as “infertility indicator gene products”; and genes encoding the response indicator gene products are referred to as “infertility indicator genes.” Normalized expression levels of one or more of these infertility indicator genes can be determined to assess a female patient for an in vitro fertilization treatment cycle. Infertility indicator genes were identified as described in detail below in the Examples. Other genes that are suitable for use in the analysis can be identified using the methods described here in the Examples section.

In carrying out a subject assessment, a sample comprising an infertility indicator gene is assayed for a level of an infertility indicator gene product(s). Where the gene product being assayed is a nucleic acid, a nucleic acid sample (e.g., a sample comprising nucleic acid) is obtained from an embryo cell. Where the gene product being assayed is a protein, a polypeptide sample (e.g., a sample comprising polypeptides) is obtained from an embryo.

Nucleic acid (including mRNA) and/or polypeptide infertility indicator gene products can be obtained from an embryo, including an oocyte, such as an arrested embryo or oocyte (e.g., an embryo or oocyte having less than about 8 cells on about day 3 following fertilization, including about 7 cells, about 6 cells, about 5 cells, about 4 cells, about 3 cells, etc.), using standard methods. Levels of nucleic acid and/or polypeptide gene products can be measured using any of a variety of well-known methods, including those described in the Examples below.

An expression level of a response indicator gene is normalized relative to the level of an expression product of a reference gene(s). Assessing the infertility likelihood is conducted by comparing the normalized expression level to a range of values of normalized expression levels of the gene product in an embryo cell.

Normalized expression level of one or more infertility indicator genes can be carried out to assess the likelihood that a patient will respond positively or negatively to an in vitro fertilization treatment cycle. Normalized expression level of a single infertility indicator gene can be carried out to assess the likelihood that a patient will respond positively or negatively to an in vitro fertilization treatment cycle. In addition, normalized expression level of two or more infertility indicator genes can be carried out to assess the likelihood that a patient will respond positively or negatively to an in vitro fertilization treatment cycle. The analysis can be more stringent, e.g., the optimal number of embryos to transfer to the female patient to maximize the likelihood of a live birth outcome while minimizing the likelihood of multiple gestations. The analysis can be less stringent, e.g., the likelihood that a patient will exhibit a beneficial response to an in vitro fertilization treatment cycle.

In some embodiments, the analysis includes determining the optimal number of embryos to transfer in order to minimize the probability of multiple gestation events in a subject. In such embodiments, the subject is first identified as a subject having a high probability of having multiple gestation events. The subject is then analyzed to determine the optimal number of embryos to transfer in order to provide for a single live birth event following the in vitro fertilization cycle.

It will be appreciated that assessment of likelihood that a patient will respond positively or negatively in vitro fertilization treatment cycle can be conducted by determining normalized expression levels of two or more infertility indicator genes (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more infertility indicator genes), or any combination of one or more sets of infertility indicator genes. The assessment can involve analyzing expression levels of a combination of infertility indicator genes, and determining normalized expression levels of the combination of infertility indicator genes, where the infertility indicator gene products can include gene products that are positively correlated with an in vitro fertilization treatment cycle and gene products that are negatively correlated with an in vitro fertilization treatment cycle. For example, a normalized level of a first gene that positively correlates with an in vitro fertilization treatment cycle, and a normalized level of a second gene that negatively correlates with an in vitro fertilization treatment cycle, can be determined.

Determining a Normalized Level of a Gene Product

As discussed above, the expression level of an infertility indicator gene is normalized, thereby providing a normalized value. The expression level of an infertility indicator gene is normalized relative to the level of an expression product of a reference gene(s).

For example, the expression level of an infertility indicator gene can be normalized relative to the mean level of gene products of two or more reference genes. As an example, the expression level of an infertility indicator gene can be normalized relative to the mean level of gene products of all assayed genes, or a subset of the assayed genes, where a subset of the assayed genes can include 3, 4, 5, 6, 7, 8, 9, or more assayed genes.

Suitable reference genes include, but are not limited to, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (see, e.g., GenBank Accession No. NM_(—)002046; phosphoglycerate kinase 1 (see, e.g., GenBank Accession No. NM_(—)000291); lactate dehydrogenase A (see, e.g., GenBank Accession No. NM_(—)005566); ribosomal protein L32 (see, e.g., GenBank Accession No. NM_(—)000994); ribosomal protein S18 (see, e.g., GenBank Accession No. NM_(—)022551); tubulin, beta polypeptide (TUBB) (see, e.g., GenBank Accession No. NM_(—)001069); and beta actin (see, e.g., GenBank Accession No. NM_(—)001101). See, e.g., Eisenberg and Levanon (2003) Trends in Genetics 19:362, for a list of additional suitable reference genes.

The level of an RNA transcript as measured by TaqMan® RT-PCR refers to the cycle threshold (Ct) value. The lower the Ct, the greater the amount of mRNA present in the sample. The expression value of a RNA transcript in a sample is normalized, e.g., by first determining the mean expression value in Ct of designated reference genes in a sample (Ct_(Ref)). The normalized expression value for a gene (Ct_(Gene)) is then calculated as Ct_(Gene)-Ct Ct_(Ref). Optionally, the normalized expression values for all genes can be adjusted, e.g., so that all adjusted normalized Ct have a value >0.

Determining a Probability of Beneficial Response

A normalized level of an infertility indicator gene product determined for an individual patient can be compared to normalized expression level values for the infertility indication gene determined in a population of patients for which the clinical outcome is already known in order to determine an individual patient's probability of beneficial response to an in vitro fertilization treatment cycle. Normalized expression level values (e.g., expressed as Ct) correlated with a probability can be used. For example, a normalized level of a response indicator gene product can be compared graphically, to determine the probability of beneficial response to an in vitro fertilization treatment cycle.

The analyses and determinations described herein in connection with a subject method for assessing likelihood of response can be made without the need for assessing any change in the level of a response indicator gene over time.

Classification Tree Analysis

One approach to analyze this data is to use a classification tree algorithm that searches for patterns and relationships in large datasets. A “classification tree” is a recursive partition to evaluate a female subject for an in vitro fertilization procedure using a series of questions that are designed to accurately place the patient into one of the classes. Each question asks whether a patient's condition satisfies a given predictor, with each answer being used to guide the user down the classification tree until a class into which the patient falls can be determined. As used herein, a “predictor” is the range of values of the features—such as, for example, age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, and number of 8-cell embryos transferred.

Multiple Additive Regression Trees

An automated, flexible modeling technique that uses multiple additive regression trees (MART) may also be used to classify sets of features as belonging to one of two populations. A MART model uses an initial offset, which specifies a constant that applies to all predictions, followed by a series of regression trees. Its fitting is specified by the number of decision points in each tree, the number of trees to fit, and a “granularity constant” that specifies how radically a particular tree can influence the MART model. For each iteration, a regression tree is fitted to estimate the direction of steepest descent of the fitting criterion. A step having a length specified by the granularity constant is taken in that direction. The MART model then consists of the initial offset plus the step provided by the regression tree. The differences between the observed and predicted values are recalculated, and the cycle proceeds again, leading to a progressive refinement of the prediction. The process continues either for a predetermined number of cycles or until some stopping rule is triggered.

The number of splits in each tree is a particularly meaningful fitting parameter. If each tree has only one split, the model looks only at one feature and has no capability for combining two predictors. If each tree has two splits, the model can accommodate two-way interactions among features. With three trees, the model can accommodate three-way interactions, and so forth.

The value of sets of features in predicting class status was determined for data sets with features and known class status. MART provides a measure of the contribution or importance of individual features to the classification decision rule. Specifically, the degree to which a single feature contributes to the decision rule upon its selection at a given tree split can be measured to provide a ranking of features by their importance in determining the final decision rule. Repeating the MART analysis on the same data set may yield a slightly different ranking of features, especially with respect to those features that are less important in establishing the decision rule. Sets of predictive features and their corresponding biomarkers that are useful for the present invention, therefore, may vary slightly from those set forth herein.

One exemplary implementation of the MART technology is found in a module, or “package,” for the R statistical programming environment (see Venables et al., in Modern Applied Statistics with S, 4th ed. (Springer, 2002); www.r-project.org). Results reported in this document were calculated using R versions 1.7.0 and 1.7.1. The module implementing MART, written by Dr. Greg Ridgeway, is called “gbm” and is also available for download (see www.r-project.org). The MART algorithm is amenable to ten-fold cross-validation. The granularity parameter was set to 0.05, and the gbm package's internal stopping rule was based on leaving out 20% of the data cases at each marked iteration. The degree of interaction was set to one, so no interactions among features were considered. The gbm package estimates the relative importance of each feature on a percentage basis, which cumulatively equals 100% for all the features of the biomarker profile. The features with highest importance, which together account for at least 90% of total importance, are reported as potentially having predictive value. Note that the stopping rule in the fitting of every MART model contributes a stochastic component to model fitting and feature selection. Consequently, multiple MART modeling runs based on the same data may choose slightly, or possibly even completely, different sets of features. Such different sets convey the same predictive information; therefore, all the sets are useful in the present invention. Fitting MART models a sufficient number of times is expected to produce all the possible sets of predictive features within a profile. Accordingly, the disclosed sets of predictors are merely representative of those sets of features that can be used to classify individuals into populations.

Wilcoxon Signed Rank Test Analysis

In yet another method, a nonparametric test such as a Wilcoxon Signed Rank Test can be used to identify individual biomarkers of interest. The features in a biomarker profile are assigned a “p-value,” which indicates the degree of certainty with which the biomarker can be used to classify individuals as belonging to a particular reference population. Generally, a p-value having predictive value is lower than about 0.05. Biomarkers having a low p-value can be used by themselves to classify individuals. Alternatively, combinations of two or more biomarkers can be used to classify individuals, where the combinations are chosen on the basis of the relative p-value of a biomarker. In general, those biomarkers with lower p-values are preferred for a given combination of items of information. Combinations of at least three, four, five, six, 10, 20 or 30 or more biomarkers also can be used to classify individuals in this manner. The artisan will understand that the relative p-value of any given biomarker may vary, depending on the size of the reference population.

Analysis Results Reporting

As discussed above, evaluation of a female subject for an in vitro fertilization procedure, including determining probability of a live birth event, is done by obtaining and comparing items of information from the female subject to a library of known profile patterns known to be indicative of responsiveness to an in vitro fertilization procedure using an algorithm based upon said preselected patient variables and optionally evaluating the normalized expression level of one or more fertility response genes. In some embodiments, a patient's evaluation is provided in a report. Thus, in some embodiments, the method further includes a step of preparing or generating a report that includes information regarding the patient's likelihood of successes for an in vitro fertilization procedure. For example, a subject method can further include a step of generating or outputting a report providing the results of a patient's evaluation, which report can be provided in the form of an electronic medium (e.g., an electronic display on a computer monitor), or in the form of a tangible medium (e.g., a report printed on paper or other tangible medium).

A report that includes information regarding the patient's evaluation is provided to a user. The evaluation may include, for example, a determination of success for implantation of embryos, selection of an optimal number of embryos to transfer, and determination of success in subsequent in vitro fertilization treatment cycles following an unsuccessful treatment cycle.

The report generator may also perform one or more of sample gathering, sample processing, and data generation, e.g., the report generator may also perform one or more of: a) sample gathering; b) sample processing; c) measuring a level of an infertility indicator gene product(s); d) measuring a level of a reference gene product(s); and e) determining a normalized level of a infertility indicator gene product(s). Alternatively, an entity other than the report generator can perform one or more sample gathering, sample processing, and data generation.

For clarity, it should be noted that the term “user,” which is used interchangeably with “client,” is meant to refer to a person or entity to whom a report is transmitted, and may be the same person or entity who does one or more of the following: a) collects a sample; b) processes a sample; c) provides a sample or a processed sample; and d) generates data (e.g., level of a response indicator gene product(s); level of a reference gene product(s); normalized level of a response indicator gene product(s)) for use in the likelihood assessment. In some cases, the person(s) or entity(ies) who provides sample collection and/or sample processing and/or data generation, and the person who receives the results and/or report may be different persons, but are both referred to as “users” or “clients” herein to avoid confusion. In certain embodiments, e.g., where the methods are completely executed on a single computer, the user or client provides for data input and review of data output. A “user” can be a health professional (e.g., a clinician, a laboratory technician, a physician (e.g., a Reproductive Endocrinologist), etc.).

In embodiments where the user only executes a portion of the method, the individual who, after computerized data processing according to the methods of the invention, reviews data output (e.g., results prior to release to provide a complete report, a complete, or reviews an “incomplete” report and provides for manual intervention and completion of an interpretive report) is referred to herein as a “reviewer.” The reviewer may be located at a location remote to the user (e.g., at a service provided separate from a healthcare facility where a user may be located).

Report

A “report,” as described herein, is an electronic or tangible document which includes report elements that provide information of interest relating to a subject likelihood assessment and its results. A subject report includes at least an evaluation for an in vitro fertilization treatment cycle, e.g., facilitate a determination of success for implantation of embryos, selection of an optimal number of embryos to transfer, and determination of success in subsequent in vitro fertilization treatment cycles following an unsuccessful treatment cycle. A subject report can be completely or partially electronically generated. A subject report can further include one or more of: 1) information regarding the testing facility; 2) service provider information; 3) patient data; 4) sample data; 5) an interpretive report, which can include various information including: a) indication; b) test data, where test data can optionally include normalized level of one or more infertility indicator gene products; and 6) other features.

Where government regulations or other restrictions apply (e.g., requirements by health, malpractice, or liability insurance), all results, whether generated wholly or partially electronically, are subjected to a quality control routine prior to release to the user.

Testing Facility Information

The report can include information about the testing facility, which information is relevant to the hospital, clinic, or laboratory in which sample gathering and/or data generation was conducted. Data generation can include one or more of: a) measuring a level of a gene product(s) (e.g., an infertility indicator gene product(s), a reference gene product(s)); b) determination of a normalized level of an infertility indicator gene product. This information can include one or more details relating to, for example, the name and location of the testing facility, the identity of the lab technician who conducted the assay and/or who entered the input data, the date and time the assay was conducted and/or analyzed, the location where the sample and/or result data is stored, the lot number of the reagents (e.g., kit, etc.) used in the assay, and the like. Report fields with this information can generally be populated using information provided by the user.

Service Provider Information

The report can include information about the service provider, which may be located outside the healthcare facility at which the user is located, or within the healthcare facility. Examples of such information can include the name and location of the service provider, the name of the reviewer, and where necessary or desired the name of the individual who conducted sample gathering and/or data generation. Report fields with this information can generally be populated using data entered by the user, which can be selected from among pre-scripted selections (e.g., using a drop-down menu). Other service provider information in the report can include contact information for technical information about the result and/or about the interpretive report.

Patient Data

The patient data can include patient medical history (which can include, e.g., data about prior or current in vitro fertilization treatment cycles), personal history; administrative patient data (that is, data that are not essential to the likelihood assessment), such as information to identify the patient (e.g., name, patient date of birth (DOB), gender, mailing and/or residence address, medical record number (MRN), room and/or bed number in a healthcare facility), insurance information, and the like), the name of the patient's physician or other health professional who ordered the response likelihood assessment and, if different from the ordering physician, the name of a staff physician who is responsible for the patient's care (e.g., primary care physician). Report fields with this information can generally be populated using data entered by the user.

Exemplary items of information include, but are not limited to: patient characteristics, such as age, previous infertility history, clinical diagnosis; clinical treatment information, such as type of medication, number of days of stimulation, number of oocytes, etc.; conventional embryo morphology data, such as number of embryos, developmental stage, grade, and the like. In some embodiments, the information includes age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, number of 8-cell embryos transferred, age, diminished ovarian reserve, endometrial thickness, blastocyst rate, total number of embryos, total number of oocytes, total amount of gonatropins administered, and number of total motile sperm.

Sample Data

The sample data can provide information about the embryo analyzed in the likelihood assessment, such as the number of days following fertilization resulting in arrest, and the date and time collected. Report fields with this information can generally be populated using data entered by the user, some of which may be provided as pre-scripted selections (e.g., using a drop-down menu).

Interpretive Report

The interpretive report portion of the report includes information generated after processing of the data as described herein. The interpretive report can include an evaluation of a female subject for an in vitro fertilization procedure. The interpretive report can include, for example, Result of analysis comparing the profile for the female subject to a library of known profile patterns known to be indicative of responsiveness to an in vitro fertilization procedure using an algorithm based upon said preselected patient variables, and optionally Result of normalized level of infertility indicator gene(s) (e.g., “normalized level of infertility indicator gene(s)”); Interpretation; and, optionally, Recommendation(s).

The Interpretation portion of the report can include a Recommendation(s). Where the results indicate a determination of success for implantation of embryos, selection of an optimal number of embryos to transfer, and determination of success in subsequent in vitro fertilization treatment cycles following an unsuccessful treatment cycle.

It will be readily appreciated that the report can include all or some of the elements above, with the proviso that the report generally includes at least the elements sufficient to provide the analysis requested by the user (e.g., likelihood assessment).

Additional Features

It will also be readily appreciated that the reports can include additional elements or modified elements. For example, where electronic, the report can contain hyperlinks which point to internal or external databases which provide more detailed information about selected elements of the report. For example, the patient data element of the report can include a hyperlink to an electronic patient record, or a site for accessing such a patient record, which patient record is maintained in a confidential database. This latter embodiment may be of interest in an in-hospital system or in-clinic setting.

Computer-Based Systems and Methods

The methods and systems described herein can be implemented in numerous ways. In one embodiment of particular interest, the methods involve use of a communications infrastructure, for example the internet. Several embodiments of the invention are discussed below. It is also to be understood that the present invention may be implemented in various forms of hardware, software, firmware, processors, or a combination thereof. The methods and systems described herein can be implemented as a combination of hardware and software. The software can be implemented as an application program tangibly embodied on a program storage device, or different portions of the software implemented in the user's computing environment (e.g., as an applet) and on the reviewer's computing environment, where the reviewer may be located at a remote site associated (e.g., at a service provider's facility).

The various elements of the computing device, such as a the input device, may be associated with other elements of the system via a wired connection or a wireless connection, including, for example, a wireless LAN connection, Bluetooth connection protocol, ZigBee connection protocol, radio-frequency connection protocol, or a cellular phone connection protocol, including code derived multiple access (CDMA) or via a global system for mobile communication (GSM).

For example, during or after data input by the user, portions of the data processing can be performed in the user-side computing environment. For example, the user-side computing environment can be programmed to provide for defined test codes to denote a likelihood “score,” where the score is transmitted as processed or partially processed responses to the reviewer's computing environment in the form of test code for subsequent execution of one or more algorithms to provide a results and/or generate a report in the reviewer's computing environment.

The application program for executing the algorithms described herein may be uploaded to, and executed by, a machine comprising any suitable architecture. In general, the machine involves a computer platform having hardware such as one or more central processing units (CPU), a random access memory (RAM), and input/output (I/O) interface(s). The computer platform also includes an operating system and microinstruction code. The various processes and functions described herein may either be part of the microinstruction code or part of the application program (or a combination thereof) which is executed via the operating system. In addition, various other peripheral devices may be connected to the computer platform such as an additional data storage device and a printing device.

As a computer system, the system generally includes a processor unit. The processor unit operates to receive information, which generally includes subject information data, such as age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, number of 8-cell embryos transferred, age, diminished ovarian reserve, endometrial thickness, blastocyst rate, total number of embryos, total number of oocytes, total amount of gonatropins administered, and number of total motile sperm. This information received can be stored at least temporarily in a database, and data analyzed to generate a report as described above.

Part or all of the input and output data can also be sent electronically; certain output data (e.g., reports) can be sent electronically or telephonically (e.g., by facsimile, e.g., using devices such as fax back). Exemplary output receiving devices can include a display element, a printer, a facsimile device and the like. Electronic forms of transmission and/or display can include email, interactive television, and the like. In an embodiment of particular interest, all or a portion of the input data and/or all or a portion of the output data (e.g., usually at least the final report) are maintained on a web server for access, preferably confidential access, with typical browsers. The data may be accessed or sent to health professionals as desired. The input and output data, including all or a portion of the final report, can be used to populate a patient's medical record which may exist in a confidential database at the healthcare facility.

A system for use in the methods described herein generally includes at least one computer processor (e.g., where the method is carried out in its entirety at a single site) or at least two networked computer processors (e.g., where data is to be input by a user (also referred to herein as a “client”) and transmitted to a remote site to a second computer processor for analysis, where the first and second computer processors are connected by a network, e.g., via an intranet or internet). The system can also include a user component(s) for input; and a reviewer component(s) for review of data, generated reports, and manual intervention. Additional components of the system can include a server component(s); and a database(s) for storing data (e.g., as in a database of report elements, e.g., interpretive report elements, or a relational database (RDB) which can include data input by the user and data output. The computer processors can be processors that are typically found in personal desktop computers (e.g., IBM, Dell, Macintosh), portable computers, mainframes, minicomputers, or other computing devices, such as Smartphone devices, including, for example, an Apple® iPhone® device.

The networked client/server architecture can be selected as desired, and can be, for example, a classic two or three tier client server model. A relational database management system (RDMS), either as part of an application server component or as a separate component (RDB machine) provides the interface to the database.

In one embodiment, the architecture is provided as a database-centric client/server architecture, in which the client application generally requests services from the application server which makes requests to the database (or the database server) to populate the report with the various report elements as required, particularly the interpretive report elements, especially the interpretation text and alerts. The server(s) (e.g., either as part of the application server machine or a separate RDB/relational database machine) responds to the client's requests.

The input client components can be complete, stand-alone personal computers offering a full range of power and features to run applications. The client component usually operates under any desired operating system and includes a communication element (e.g., a modem or other hardware for connecting to a network), one or more input devices (e.g., a keyboard, mouse, keypad, or other device used to transfer information or commands), a storage element (e.g., a hard drive or other computer-readable, computer-writable storage medium), and a display element (e.g., a monitor, television, LCD, LED, or other display device that conveys information to the user). The user enters input commands into the computer processor through an input device. Generally, the user interface is a graphical user interface (GUI) written for web browser applications.

The server component(s) can be a personal computer, a minicomputer, or a mainframe and offers data management, information sharing between clients, network administration and security. The application and any databases used can be on the same or different servers.

Other computing arrangements for the client and server(s), including processing on a single machine such as a mainframe, a collection of machines, or other suitable configuration are contemplated. In general, the client and server machines work together to accomplish the processing of the present invention.

Where used, the database(s) is usually connected to the database server component and can be any device which will hold data. For example, the database can be a any magnetic or optical storing device for a computer (e.g., CDROM, internal hard drive, tape drive). The database can be located remote to the server component (with access via a network, modem, etc.) or locally to the server component.

Where used in the system and methods, the database can be a relational database that is organized and accessed according to relationships between data items. The relational database is generally composed of a plurality of tables (entities). The rows of a table represent records (collections of information about separate items) and the columns represent fields (particular attributes of a record). In its simplest conception, the relational database is a collection of data entries that “relate” to each other through at least one common field.

Additional workstations equipped with computers and printers may be used at point of service to enter data and, in some embodiments, generate appropriate reports, if desired. The computer(s) can have a shortcut (e.g., on the desktop) to launch the application to facilitate initiation of data entry, transmission, analysis, report receipt, etc. as desired.

Computer-Readable Storage Media

The invention also contemplates a computer-readable storage medium (e.g. CD-ROM, memory key, flash memory card, diskette, etc.) having stored thereon a program which, when executed in a computing environment, provides for implementation of algorithms to carry out all or a portion of the methods of analysis of evaluating a subject for an in vitro fertilization procedure as described herein. Where the computer-readable medium contains a complete program for carrying out the methods described herein, the program includes program instructions for collecting, analyzing and generating output, and generally includes computer readable code devices for interacting with a user as described herein, processing that data in conjunction with analytical information, and generating unique printed or electronic media for that user.

Where the storage medium provides a program which provides for implementation of a portion of the methods described herein (e.g., the user-side aspect of the methods (e.g., data input, report receipt capabilities, etc.)), the program provides for transmission of data input by the user (e.g., via the internet, via an intranet, etc.) to a computing environment at a remote site. Processing or completion of processing of the data is carried out at the remote site to generate a report. After review of the report, and completion of any needed manual intervention, to provide a complete report, the complete report is then transmitted back to the user as an electronic document or printed document (e.g., fax or mailed paper report). The storage medium containing a program according to the invention can be packaged with instructions (e.g., for program installation, use, etc.) recorded on a suitable substrate or a web address where such instructions may be obtained. The computer-readable storage medium can also be provided in combination with one or more reagents for carrying determining subject information data, e.g., material for determining rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, and number of 8-cell embryos transferred, and the like.

Kits

The materials for use in the methods of the present invention are suited for preparation of kits produced in accordance with well known procedures. The invention thus provides kits comprising reagents, which may include gene-specific or gene-selective probes and/or primers useful for assaying the expression of genes disclosed herein and for assessing the likelihood of response to an in vitro treatment cycle.

For example, a subject kit can include one or more nucleic acid probes that hybridize specifically to nucleic acid infertility indicator gene products. A subject kit can include, e.g., one or more nucleic acid probes, where each of the one or more probes hybridizes specifically to a different response indicator gene product. For example, a subject kit can include probes that hybridize specifically to nucleic acid products of infertility indicator genes including, but are not limited to, Oct4, Eif3c, Papola, Piwil2, Eif3b, Eif4b, Rbm3, and Cpsf4. As another example, a subject kit can include a set of two or more nucleic acid probes, where each probe of the set hybridizes to a nucleic acid product of a different infertility indicator gene. For example, a subject kit can include a set of two, three, four, five, six, seven, or more, nucleic acid probes, where each probe of the set hybridizes to a nucleic acid product of a different member of a set of infertility indicator genes.

In some cases, a subject kit will include, in addition to a probe that hybridizes specifically to a nucleic acid product of an infertility indicator gene, one or more probes that hybridize specifically to a reference gene product. Such probes can be used in determining normalized expression levels of an infertility indicator gene.

A subject kit can include one or more nucleic acid primer pairs, where the primer pairs, when used as primers in a polymerase chain reaction, amplify a target nucleic acid response indicator gene product, or a target region of a nucleic acid response indicator gene product. A subject kit can include primer pairs for multiple infertility indicator genes.

Exemplary sequences of nucleic acid primers and probes are provided in the Examples described herein. Those skilled in the art will readily appreciate that other probe and primer sequences are also possible, and are readily obtained based on known nucleotide sequences of infertility indicator genes, and/or based on known nucleotide sequences of reference genes.

In addition to the above-mentioned probes and primers, a subject kit can comprise reagents for the extraction and/or isolation of RNA from single cell embryos, in particular fixed paraffin-embedded tissue samples and/or reagents for preparing a cDNA copy of an mRNA, and/or reagents for nucleic acid amplification. Exemplary reagents include those required for use of a FLUIDIGM® BIOMARK® 48.48 Dynamic array system, comparable single-cell gene expression analysis platform (RT-PCR), or emerging technology such as next-generation, whole-transcriptome sequencing at the single-cell level.

Primers and probes can be designed based on known sequences of infertility indicator genes, and are readily synthesized by standard techniques, e.g., solid phase synthesis via phosphoramidite chemistry, as disclosed in U.S. Pat. Nos. 4,458,066 and 4,415,732, incorporated herein by reference; Beaucage et al. (1992) Tetrahedron 48:2223-2311; and Applied Biosystems User Bulletin No. 13 (1 Apr. 1987). Other chemical synthesis methods include, for example, the phosphotriester method described by Narang et al., Meth. Enzymol. (1979) 68:90 and the phosphodiester method disclosed by Brown et al., Meth. Enzymol. (1979) 68:109. Poly(A) or poly(C), or other non-complementary nucleotide extensions may be incorporated into probes using these same methods. Hexaethylene oxide extensions may be coupled to probes by methods known in the art. Cload et al. (1991) J. Am. Chem. Soc. 113:6324-6326; U.S. Pat. No. 4,914,210 to Levenson et al.; Durand et al. (1990) Nucleic Acids Res. 18:6353-6359; and Horn et al. (1986) Tet. Lett. 27:4705-4708.

A probe or a primer can include a detectable label. Exemplary labels include fluorochromes, e.g. fluorescein isothiocyanate (FITC), rhodamine, Texas Red, phycoerythrin, allophycocyanin, 6-carboxyfluorescein (6-FAM), 2′,7′-dimethoxy-4′,5′-dichloro-6-carboxyfluorescein (JOE), 6-carboxy-X-rhodamine (ROX), 6-carboxy-2′,4′,7′,4,7-hexachlorofluorescein (HEX), 5-carboxyfluorescein (5-FAM), N,N,N′,N′-tetramethyl-6-carboxyrhodamine (TAMRA), Cy5, Cy3, and the like; and radioactive labels (e.g., ³²P, etc.).

Probes and primers for inclusion in a subject kit include those useful in various amplification and/or detection systems. Exemplary amplification and/or detection systems include Sunrise™ primer-based systems, Molecular Beacons, the Taqman™ system, an Amplifluor™ hairpin primer-based system, a Scorpions technology (e.g., bi-functional molecules containing a PCR primer element covalently linked to a probe element), a Light Upon Extension or LUX™-based system, and a FLUIDIGM® BIOMARK® 48.48 Dynamic array system. Further exemplary detection systems include those based on a melt-curve analysis, and using intercalating dyes such as the fluorescent dye SYBR Green.

The kits may optionally comprise reagent(s) with an identifying description or label or instructions relating to their use in the methods of the present invention. The kits may comprise containers (including microtiter plates suitable for use in an automated implementation of the method), each with one or more of the various reagents (typically in concentrated form) utilized in the methods of the invention, including, for example, pre-fabricated microarrays, buffers, the appropriate nucleotide triphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one or more probes and primers of the present invention (e.g., appropriate length poly(T) or random primers linked to a promoter reactive with the RNA polymerase).

Instructions for the use of mathematical algorithms used to evaluate a female subject for an in vitro fertilization treatment cycle, including determining a probability of a live birth event, can also be included in a subject kit. In such embodiments, the kits will further include a written or electronic medium, or instructions to access a remote database, as described above, to provide and/or receive information, which generally includes subject information data, such as age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, number of 8-cell embryos transferred, age, diminished ovarian reserve, endometrial thickness, blastocyst rate, total number of embryos, total number of oocytes, total amount of gonatropins administered, and number of total motile sperm, in order to carry out the methods as described above.

EXAMPLES

The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric.

Materials and Methods

The following methods and materials were used in the examples below.

Data Collection, Inclusion and Exclusion Criteria

Data related to clinical diagnoses, UVF treatment protocol and monitoring, embryology data and treatment outcomes for all IVF cycles performed between Jan. 1, 2003 and Dec. 31, 2006 at Stanford University Medical Center were retrieved from BabySentryPro (BabySentry Ltd, Limassol, Cyprus), a widely used fertility database management system, or obtained from medical and embryology records as necessary. Retrospective data collection, de-identification, and analysis were performed according to a Stanford University Institutional Review Board-approved protocol. The inclusion criteria for data analysis were fresh, stimulated, non-donor oocyte IVF cycles.

In certain experiments, cycles that did not result in embryo transfer for any reason, cycles performed for women aged over 45, and those performed for preimplantation genetic screening were excluded.

In other experiments, we did not exclude cycles that were canceled at any point due to medical or non-medical reasons after the IVF treatment had started. We excluded cryopreserved embryo transfer cycles which used embryos that had been conceived in a different IVF clinic.

Defining Cycle Numbers

We renumbered all IVF cycles according to the following method. For each patient, the first fresh IVF cycle appearing in this four-year data set is called “Cycle 1”. The final outcome of all embryo transfer treatments that utilize fresh or cryopreserved embryos conceived from Cycle 1 is defined as the outcome for Cycle 1. The second fresh IVF cycle that appears is defined “Cycle 2”, and so on. Our database could not accommodate data on IVF cycles that were performed elsewhere.

Assessment of Embryo Development

The standard clinical protocols for IVF treatment, fertilization, embryo culture, embryo assessment, cryopreservation criteria, and clinical outcomes are described below. The normal progression of human embryo development in vitro is characterized by the appearance of 2 pronuclei at 16-20 hours after insemination as evidence of fertilization on Day 1, with Day 0 as the day of oocyte retrieval. By late Day 1, embryo development has reached the 2-cell stage, followed by the 4-cell and 8-cell stages on Days 2 and 3, respectively. On Days 4 and 5, embryo development is characterized by the establishment of the morula and blastocyst stages, respectively. All embryos were available for evaluation on Day 3. The day of embryo transfer was determined by the number of blastomeres on Day 3. In general, if 4 or more 8-cell embryos were present, we would recommend extended embryo culture until Day 5, when blastocyst transfer, which has been associated with higher pregnancy rates, would be performed. If fewer than four 8-cell embryos were present, embryo transfer would be performed on Day 3.

Patient, IVF Cycle, and Embryo Parameters

30 variables for association with IVF treatment outcomes were analyzed, as listed in Table 1, under four main categories: patient characteristics and clinical diagnoses, IVF cycle characteristics, embryo cohort parameters, and parameters of transferred embryos. The cleavage arrest rate was defined as the percentage of embryos within a cohort with 4 or fewer cells on Day 3 of in vitro culture. All other variables were self-explanatory.

DEFINITION OF OUTCOMES

Statistical analyses were performed based on the dichotomous outcomes of live birth versus no live birth. No live birth encompassed all other outcomes such as negative serum β-hCG, or positive serum β-hCG followed by biochemical pregnancy, spontaneous abortion, and ectopic pregnancy.

Statistical Analysis

Since some patients underwent more than one IVF cycle during the study period, the analyses were performed based on treatment cycles rather than patients. Statistical analyses were performed based on the dichotomous outcomes of no pregnancy, as defined by negative serum β-hCG, and pregnancy, as defined by positive serum β-hCG, and included biochemical pregnancy, clinical pregnancy, spontaneous abortion, and ectopic pregnancy. We performed pair-wise logistic regression of each variable to the outcome and determined the Pearson correlation coefficient between each pair of continuous variables.

For the main analyses, boosted classification trees were constructed by MART® to identify non-redundant prognostic variables, which were then further analyzed by CART to identify thresholds that would define them as categorical variables. MART® is a robust method used to identify interactive structure of variables that are predictive of outcomes. The use of cross-validation and boosting in parameter selection and model assessment in MART® also preserve parsimony and prevent over-fitting. In the MART® tree constructions, the whole data set is divided into 10 subsets to achieve 10 fold cross validation for model assessment. The same 10 fold cross validation was repeated 1000 times to perform a robust prediction rate estimation and identify tree models with the highest prediction rates in the CART. While MART® is powerful in selecting non-redundant prognostic variables from a large set of highly interactive variables, CART analysis results in simple algorithms, and more easily understood “decision trees”, that are used in the medical literature (Guznick et al., N Engl J Med 345: 1388-1393. (2001)). Thus non-redundant, prognostic variables identified by MART® to confer prediction were analyzed by CART to further define prognostic thresholds.

In some experiments, if patients underwent multiple fresh IVF cycles during the study period, only the first three cycles were analyzed. We generated the models based on cycle 1 (C1) data only. Data from C2 and C3 were used to test inter-cycle validation of the pre-transfer model only.

In such experiments, we performed pair-wise logistic regression of each variable to the outcome and determined the Pearson correlation coefficient between each pair of continuous variables. We generated three models based on data that were available at three different time points prior to IVF treatment (pre-IVF), oocyte retrieval (pre-OR), and after embryo transfer (post-IVF). We generated each model by ranking variables according to their relative influence using gradient boosting machine (GBM), the R-software implementation of MART®, followed by construction of regression tree models using top-ranked variables with Rpart software. MART® is a robust method used to identify interactive structure of variables that are predictive of outcomes. The use of cross-validation and boosting in parameter selection and model assessment in MART® also preserve parsimony and prevent over-fitting. In the MART® tree constructions, the whole data set is divided into 10 subsets to achieve 10 fold cross validation for model assessment. The same 10 fold cross validation was repeated 1000 times to perform a robust prediction rate estimation and identify tree models with the highest prediction rates. While MART® is powerful in selecting non-redundant prognostic variables from a large set of highly interactive variables.

Treatment Protocols Used for Assisted Reproductive Technologies (ART)

The majority of our analyzed IVF cycles were performed in patients with poor ovarian reserve, severe male factor infertility, tubal infertility, anovulatory disorders, or unexplained etiology. In general, one of three stimulation protocols was used in each treatment cycle: luteal downregulation (long) was used for most patients, and microdose lupron (flare) and antagonist protocols were used primarily for patients with presumed diminished ovarian reserve or with a history of previously failed IVF cycles. The long protocol consisted of luteal downregulation using 0.5 mg leuprolide acetate, which was decreased to 0.25 mg with stimulation. In the flare protocol, microdose lupron (0.04 mg s.c. bid) was started after 2-4 weeks of oral contraceptive pills. In the antagonist protocol, GnRH antagonist was initiated when the lead follicle reached 14 mm in size. In all three protocols, baseline ultrasound testing was performed to document that no cysts >1.5 cm were present in the ovaries. When baseline criteria were met, gonadotropin therapy using recombinant FSH with human menopausal gonadotropin was begun. Stimulation was generally achieved using daily dosing of a total of 150-600 IU per day in order to maximize follicular recruitment. Ultrasound monitoring of follicular growth was performed starting on cycle day 7 and then every 1-3 days as indicated. Serum estradiol levels were monitored as necessary.

A dose of 10,000 IU of human chorionic gonadotropin was administered when at least two follicles reached an average diameter of >17 mm. Transvaginal ultrasound-guided oocyte retrieval was performed 34-36 hours after hCG administration in the standard fashion with monitored anesthetic care.

Oocyte Fertilization and Embryo Culture

Oocytes were cultured in groups before fertilization under mineral oil in approximately 125 μl droplets of Sage Cleavage Medium (Cooper Surgical, Inc, Trumbull, Conn.) with 10% Serum Protein Substitute (SPS, Irvine Scientific, Santa Ana, Calif.). Oocytes destined for conventional IVF were cultured in groups of 5 and oocytes destined for intracytoplasmic sperm injection (ICSI) were cultured in groups of up to 20 after stripping the cumulus cells. Oocytes were inseminated with sperm if the semen analysis was normal and fertilization was expected to be normal. Oocytes were inseminated conventionally between 4-6 hours after retrieval. If the semen analysis was abnormal or poor fertilization was expected, then the oocytes were injected with sperm using ICSI. The fertilized oocytes were cultured in groups of up to 20 under mineral oil in approximately 125 μl droplets of Sage Cleavage Medium (Cooper Surgical, Inc, Trumbull, Conn.) with 10% SPS at 37° C. in a humidified atmosphere of 5% O₂, 5% CO₂ and 90% N₂. Fertilization check was performed 16˜18 hours after insemination or ICSI. The zygotes with clear two pronuclei were cultured for another 48 hours in Sage Cleavage Medium with 10% SPS. Oocytes with single pronucleus (1PN) or three or more pronuclei were considered abnormally fertilized. If Day 5 blastocyst transfer was indicated, extended embryo culture was be performed in Quinn's Advantage Blastocyst medium (Cooper Surgical) with 10% SPS for 48 hours before transfer. Of note, the same culture media was used during the study time period.

Cleavage and Grading of Embryos

A single team of experienced embryologists evaluated the embryos on post-retrieval day 3, 68 to 72 hours after oocyte harvest. Embryos were examined for cleavage (cell number) and grade, which includes cytoplastmic fragmentation. Embryos were graded as follows on Day 3: Grade 1, blastomeres have equal size and no cytoplasmic fragmentation; Grade 2, blastomeres have equal size and minor cytoplasmic fragmentation involving <10% of the embryo; Grade 3, blastomeres have unequal size and fragmentation involving 10-20% of the embryo; Grade 4, blastomeres have equal or unequal size, and moderate to significant cytoplasmic fragmentation covering 20-50% of the embryo; and Grade 5, few blastomeres and severe fragmentation covering ≧50% of the embryo (Veeck et al., (1999) An Atlas of Human Gametes and Conceptuses. New York: Parthenon Publishing. 47-50). Of note, cytoplasmic fragmentation in embryos was easily differentiated from cleavage based on the size of the fragments, their location within the embryo, and the absence of a nucleus. In contrast, cytoplasmic fragmentation of oocytes was not included as a variable because it was extremely rare. The presence or absence of compaction was routinely noted by our embryologists on Day 3. As compaction was observed in <10% of embryos, we did not include this variable in the analysis.

Assisted Hatching

Indications for assisted hatching (AH) in our center were advanced maternal age, elevated FSH level, and/or a history of multiple failed assisted reproduction cycles. On the day of embryo transfer, embryos for hatching were placed in phosphate-buffered saline (PBS) with 10% SPS. AH was accomplished by using the ZILOS-tk laser (Hamilton Thorne Biosciences, Beverly, Mass.) to make a hole in an area of the zona pellucida that was between blastomeres. Embryos were then rinsed and returned to the media until transfer.

Embryo Transfer and Cryopreservation

Ultrasound-guided embryo transfer was performed using a Tefcat or Echotip Softpass catheter (Cook Ob/Gyn, Spencer, Ind.). Progesterone supplementation with vaginal suppositories was performed in all patients. For patients having embryo transfer on Day 3, any remaining embryos with more than five blastomeres were placed in extended culture for another 2 or 3 days. Any expanding, expanded and hatching blastocysts with good inner cell mass and trophectoderm were frozen on day 5 or day 6. In addition, cryopreservation was performed on excess embryos, severe ovarian hyperstimulation syndrome, and fertility preservation due to medical or social reasons. Excess embryos that were not transferred were commonly discarded if they were not of sufficient quality for cryopreservation or if patients did not opt for embryo cryopreservation due to non-medical reasons. In cases of pre-implantation genetic diagnosis, embryos that tested positive for genetic diseases or aneuploidy were also discarded.

Clinical Outcomes

Serum quantitative β-hCG levels were obtained at 8-10 days after embryo transfer, and followed serially until the diagnosis of clinical pregnancy was made by the presence of a gestational sac on transvaginal ultrasound. Outcomes other than clinical pregnancy included: 1) no pregnancy if serum quantitative β-hCG was negative; 2) biochemical pregnancy as defined by decreasing serum quantitative β-hCG levels before a gestational sac could be visualized by transvaginal ultrasound; 3) spontaneous abortion as defined by pregnancy loss after a gestational sac was visualized by transvaiginal ultrasound; and 4) ectopic pregnancy; and 5) other abnormal gestations such as gestational trophoblastic disease. Live birth outcomes were obtained by follow-up contact with patients as part of routine clinical care, but they were not used in this study.

Regression Trees

Clinical IVF data, especially when considering oocyte and embryo parameters, often do not lend themselves to meaningful analysis by multivariate logistic regression. The high degree of interaction and multicollinearity of many relevant variables interfere with conventional multivariate regression. In these situations, the regression and classification tree models (CART), has been widely used in clinical research (Fonarow G C, Jama 293: 572-580 (2005); Friedman J (1999) Greedy function approximation: A stochastic boosting machine. Technical Report, Department of Statistics, Stanford University; Friedman J (1999) Stochastic gradient boosting. Technical Report, Department of Statistics, Stanford University; Friedman J (2002) Tutorial: Getting started with MART in R. Department of Statistics, Stanford University; Friedman et al., Stat Med 22: 1365-1381 (2003); Guzick et al., N Engl J Med 345: 1388-1393 (2001); Pilote et al., N Engl J Med 335: 1198-1205 (1996)). Here, we used Multiple Additive Regression Tree (MART®), a more powerful statistical method that combines “boosting” with CART to “boost” or increase accuracy in the CART method, to identify non-redundant prognostic variables.

In general, regression trees have several key advantages: 1) ability to consider all types of clinical IVF and embryology data, including numeric, ordinal, binary, and categorical variables; 2) ability to handle missing values well based on a “surrogate” splitting technique without the need for imputation; 3) ability to generate results that are invariant to monotonic data transformation and thus eliminate the need to test different methods of data transformation or metrics; 4) ability to generate trees that are immune to the effects of extreme outliers; 5) ability to generate trees that inherently explore and identify interactions of variables that would otherwise need to be explicitly stated in a multiple logistic regression. Most importantly, regression trees can consider a large number of variables, including ones that may turn out to be irrelevant, even if only a small number of variables have significant statistical impact on outcomes. This ability to consider many variables is critical for analysis of IVF outcomes, as many variables, such as percentage of 8-cell embryos, number of 8-cell embryos, percentage of 8-cell embryos transferred, and number of 8-cell embryos transferred, may be highly interactive; thus, arbitrarily selecting one of them may compromise completeness of data and introduce bias, while including all of them may cause the conventional multivariate regression to breakdown.

The results from MART® may help to identify variables that could be re-analyzed by multivariate logistic regression. Often, they may identify thresholds, or “cut-offs”, that will be used to create categorical variables to segregate cases into subgroups for further inter-group comparison of characteristics by conventional methods such as t-tests, chi-square analysis, or Wilcoxon rank sum test. For example, CART analysis was used by Guzick et al. to classify men as subfertile, of indeterminate fertile status, or fertile based on threshold values for sperm concentration, motility, and morphology, exemplifies the power of this strategy in infertility research (Guzick et al., N Engl J Med 345: 1388-1393 (2001)).

Embryo Culture

3-5 week old wild type F1 (C57BL6xDBA/2) females (Charles River) were superovulated by intraperitonial injections of 5 IU of pregnant mare's serum gonadotropin (Sigma) followed by 5 IU of human chorionic gonadotropin (Sigma) 48 hours later, and mated overnight with wild type males. Mice were sacrificed by cervical dislocation 17 hours after hCG injection, and 1-cell embryos were released from oviducts. Cumulus cells were removed by hyaluronidase (Sigma) treatment and pipetting. Pre-implantation embryos at the two pronuclei stage were recovered, pooled from 3-6 females in M2 media (Chemicon International), followed by immediate cytoplasmic microinjection and culture in Human Tubal Fluid with 10% serum supplement (In-Vitro Fertilization, Inc.) microdrops under mineral oil (Sigma) in mixed gas (90% nitrogen, 5% oxygen, 5% carbon dioxide; Praxair) at 37° C., and cultured at ten embryos per 20 μL drop.

Microinjection of Antisense Morpholino Oligonucleotides

25-nt, antisense morpholino oligonucleotides (MOs) that specifically target the 5′UTR or translational start site, or controls mismatched at 5 nts were purchased from Gene Tools, LLC. (See Table 1 for sequence details). We had determined 0.6-0.75 mM to be the maximal concentration that would allow normal rates of blastocyst development (data not shown). Hence, unless otherwise specified, 5-10 pL of 0.75 mM Ccna2-MO (0.60 mM for Oct4-MO) was injected into the cytoplasm of each embryo on an inverted microscope (Olympus IX70) equipped with hydraulic micromanipulation system (IM300 Microinjector, Narishige, Japan). 10 uninjected control embryos were used in each experiment, which was performed at least three times. The mean percentage and standard error of the mean (mean±s.e.m.) of embryos progressing to, or arresting at, each developmental stage were calculated, and statistical significance was determined by calculating the p-value using 2-tailed Student's t-test.

TABLE 1 Antisense Morpholino Oligonucleotides Target Gene-Specific Sequence in the 5′ UTR and/or Start Site GC content, Name Sequence % Ccna2-MO-1 5′-TCGAGGTGCCCGGCATCGCGGCTCC-3′ 76 (SEQ ID NO: 01) Ccna2-MO-2 5′-CTGTCGGCGGCAGAGCGTTCACAGC-3′ 68 (SEQ ID NO: 02) Ccna2-MM-1 5′-TCCAGGTCCCCCGCATCCCGGATCC-3′ 72 (SEQ ID NO: 03) Oct4-MO 5′-AGTCTGAAGCCAGGTGTCCAGCCAT-3′ 56 (SEQ ID NO: 04) Oct4-MM 5′-ACTCTCAAGCCACGTGTGCAGCGAT-3′ 56 (SEQ ID NO: 05) Oct4E4-MO 5′-CTCCGATTTGCATATCTGGGCAGGG-3′ 56 (SEQ ID NO: 06) Oct4E4-MM 5′-CTGCGATTTCCATATGTGCGCACGG-3′ 56 (SEQ ID NO: 07) Standard 5′-TCCAGGTCCCCCGCATCCCGGATCC-3′ 72 control* (SEQ ID NO: 08) * splice site of mutated human β-globin gene Mismatched nucleotides are underlined

Immunoblot and Immunocytochemistry

Injected and control embryos were collected at 2-cell stage (43 hours post human chorionic gonadotropin (hCG) administration) and washed in PBS containing 3 mg/mL polyvinylpyrrolidone (PVP). For immunoblot, injected and control embryos were lysed in RIPA buffer (50 mM Tris-HCl, pH7.5, 150 mM NaCl, 1 mM EDTA, 1% Nonident P-40, 2 mg/ml aprotonin, 2 mg/ml leupeptin, 1 mg/ml pepstain, and 20 mg/ml phenylmethylsulfonyl) containing a phosphatase inhibitor cocktail (Roche), boiled in Laemli buffer, and stored at −80° C. until lysates from 75 embryos were collected for each condition. Samples were loaded and analyzed by electrophoresis on 10% Tris-HCl polyacrylamide gel, semi-dry transferred onto nitrocellulose membrane (Bio-Rad), blocked in 0.1% Tween-20-1% Casein TBS Blocking Solution (Bio-Rad), incubated overnight in 1:250 diluted primary rabbit polyclonal anti-cyclin A2 antibody (Santa Cruz Biotechnologies, sc-751) at 4° C. and in 1:2000 diluted secondary donkey anti-rabbit horseradish peroxidase-linked antibody (Amersham, NA934V) for one hour at room temperature, and visualized using ECL Blotting Detection Reagent (Amersham). Immunocytochemistry was performed according to standard protocol. Briefly, embryos were fixed in 4% paraformaldehyde-PBS solution, permeabilized in 0.1% Triton X-PBS and treated with ImageIT FX Signal Enhancer solution (Invitrogen) at RT, incubated in 1:100 diluted primary antibody overnight at 4° C., in 1:10,000 diluted secondary antibody for one hour, followed by 3 μM DAPI for 10 min., and were mounted in VectaShield Mounting Medium (Vector Laboratories, H-1000). Controls were performed in parallel with normal rabbit or mouse serum control. All antibodies were diluted in 1% BSA. Embryos were imaged by confocal microscopy using LSM 510 Confocal Laser Scanning Microscope or epifluorescence microscopy or the Axiovert 200 microscope equipped with an Axiocam digital camera (Zeiss) using fixed parameters and exposure times. Primary antibodies were purchased from Santa Cruz Biotechnologies (anti-cyclin A2 rabbit polyclonal (sc-751), normal rabbit IgG (sc-2027), mouse monoclonal anti-Oct4 (sc-5279), and normal mouse IgG (sc-2025). Secondary antibodies were purchased from Molecular Probes (Alexa Fluor 594 goat anti-rabbit IgG (A-11012) and goat-anti mouse IgG (A-11001).

mRNA Synthesis by In Vitro Transcription

Full-length mouse cDNA clone, Oct4-pSPORT (clone ID 30019896) (Open Biosystems), and a plasmid encoding the fluorescence mitotic biosensor, a modified enhanced yellow fluorescence protein (mEYFP), were sequence-verified, linearized by restriction enzyme digest, and used as templates. 5′ capped and polyadenylated mRNA transcripts were transcribed in vitro (mMessage and PolyA-Tail kits, Ambion), which were then quantitated by UV spectroscopy, and analyzed by electrophoresis to confirm size.

RNA Sample Preparation for Gene Chip Experiments

Samples containing 20 pooled injected or control mouse embryos were washed through 3 drops of PBS/PVP and collected for total RNA extraction and isolation (Picopure Total RNA Isolation Kit, Molecular Devices Corp.), to yield 10 μL of total RNA. 5 μL of total RNA, or the equivalent of 10 mouse embryos, was subjected to two rounds of amplification (WT-Ovation Pico system, Nugen) according to manufacturer's instructions. The quality of ssDNA resulting from the second round amplification was tested on the Bioanalyzer 2100 (Agilent), and a typical yield of 5-8 μg per sample was quantitated by the ND-1000 UV spectrophotometer (Nanodrop Technologies). Direct biotin labeling and fragmentation were performed (FL-Ovation cDNA Biotin Module (Nugen). Fragmented, labeled, ssDNA samples were submitted to Stanford University PAN Core Facility for hybridization to the GeneChip® Mouse Genome 430 2.0 Array (Affymetrix), and laser scanning.

Statistical Analysis for Gene Chip Experiments

Raw data from a total of 12 gene chips (3 Ccna2-MO and their uninjected controls, and 3 Oct4-MO and their uninjected controls) and were normalized by dChip (Li C & Wong WH (2003) in The analysis of gene expression data: methods and software. (Springer, New York), pp. 120-141). Unsupervised clustering analysis was performed for genes that have: 1) expression level greater than 500 Signal Intensity (SI) in at least 10 percent of the samples; 2) standard deviation to mean ratio >0.4 and <1000 across the samples. Subsequent analyses were not restricted to these criteria. The lists of differentially expressed genes and their ranking were generated by the method proposed by Johnson and Wong, which is based on fold change, logged fold change and unpaired t-statistic (Nicholas Johnson and W.H.W. (2007) Combining scientific and statistical significance in gene ranking. Unpublished.). Differential expression was defined by a threshold of 5 percent median false discovery rate (FDR) estimated from 300 random permutations across the samples. To find significantly enriched gene ontology (GO) terms (Ashburner M, et al. (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25, 25-29), each gene list was mapped to Entrez gene identification numbers (NCBI) and tested by GOSTAT PACKAGE (Beissbarth T & Speed TP (2004) GOstat: find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics 20, 1464-1465) against a set of “universe” genes defined by “P” call in at least 2 out of 3 treated samples or 4 out of 6 control samples by (MAS, Affymetrix). To estimate the FDR, 50 tests were performed with randomly generated lists of genes from the “universe” gene set, and the average number of enriched GO terms were calculated (Ashburner et al.; Beissbarth et al.). The cut off for p-value was chosen to reflect FDR of ˜10 percent. Differentially expressed genes with possible Oct4-binding sites were identified by comparison with putative Oct4-regulated genes previously identified by Zhou et. al. (Zhou Q, Chipperfield H, Melton D A, & Wong W H (2007) A gene regulatory network in mouse embryonic stem cells. Proc Natl Acad Sci USA 104, 16438-16443), followed by mapping of probe sets to Refseq using the BIOCONDUCTOR ANNOT PACKAGE (R. C. Gentleman V J C, D. M. Bates, B. Bolstad, M. Dettling, S. Dudoit, B. Ellis, L. Gautier, Y. Ge, J. Gentry, K. Hornik, T. Hothorn, W. Huber, S. Iacus, R. Irizarry, F. Leisch, C. Li, M. Maechler, A. J. Rossini, G. Sawitzki, C. Smith, G. Smyth, L. Tierney, J. Y. H. Yang, J. Zhang. (2004) Bioconductor: Open software development for computational biology and bioinformatics. Genome Biology 5, R80).

RT-PCR, q-PCR, and Single Embryo q-PCR Analysis

Lysis buffer was added to PBS/PVP washed embryos (Cells-to-cDNA kit, Ambion) and samples were treated with 1 μL of DNAse I. Reverse transcription (RT) was performed by using 1.0 μL of SuperScript III RT enzyme (200 U/μL) as per protocol (Invitrogen). Amplification of gene-specific product by TaqPolymerase High Fidelity Kit (Invitrogen) was performed on the thermocycler (Mastercycler gradient 5331, Eppendorf) as follows: 94.0° C. for 2 min., 94.0° C. for 15 sec., 60.0° C. for 30 sec., 68.0° C. for 45 sec, 68.0° C. for 7 minutes for 50 cycles. (See Table 2 for all primer sequence and TaqMan probes). Single embryo qRT-PCR was performed using the Biomark 48.48 Dynamic Array system (Fluidigm, South San Francisco, Calif.). Single embryos were treated with acid tyrode, and collected in 10 μl reaction buffer, followed by preamplification as per manufacturer's instructions (TaqMan Gene Expression Assay, Applied Biosystems; Table S8). Amplified cDNA was loaded onto a 48.48 Dynamic Array using the NanoFlex IFC controller (Fluidigm). Threshold cycle (C_(T)) as a measurement of relative fluorescence intensity was extracted from the BioMark PCR analysis software (Fluidigm). All reactions were performed in duplicates or triplicates along with negative RT, PBS, and positive controls in at least three to five independent experiments. Data for each gene assayed were tested with a linear model (ANCOVA) in which C_(T)˜β₀+β₁*Condition+β₂*C_(T)[Gapdh]+β₃*C_(T)[beta-actin], where “Condition” referred to no injection or Oct4 knockdown. C_(T) values were directly used in data analysis, as gene expression at the single-cell level has been shown to follow a lognormal distribution.

TABLE 2 Taqman ® Probes and Gene-Specific Primers Used in q-PCR Applied Biosystems Probe Name Assay ID/Catalog No. Bmprla Mm01208758_m1 Pou5f1 Mm00658129_gH Klf9 Mm00495172_m1 Fgf4 Mm00438917_m1 Sall4 Mm01240680_m1 Bclaf1 Mm00464127_m1 Yy1 Mm00456392_m1 Pknox1 Mm00479320_m1 Gata4 Mm00484689_m1 Mta2 Mm00488671_m1 Rest1 Mm00803268_m1 Tefl5 Mm00626495_m1 Dppa5 Mm01171664_g1 Bmpr1a Mm00477650_m1 Fgfrl1 Mm00475318_g1 I117rd Mm00460340_m1 Ubtf Mm00456972_m1 Gtf3c4 Mm00557022_m1 Gtf3c2 Mm00510828_m1 Polr3e Mm00491765_m1 Polr3a Mm00805896_m1 Eif3b Mm00659801_m1 Eif3s10 Mm00468721_m1 Piwil2 Mm00502383_m1 Eif4e Mm00725633_s1 Polr2h Mm01344328_g1 Eif2c5 Mm01305462_m1 Eif3c Mm01278697_m1 Eif5b Mm01227234_m1 Papola Mm01334253_m1 Eif3e Mm01700222_g1 Sox2 Mm03053810_s1 Mouse β-actin 4352341E Mouse β-actin 4352933E Mouse GAPDH 4352932E Gene Specific Primers for Oct4 (302 bp product) Forward GGCGTTCTCTTTGGAAAGGTGTT (SEQ NO: 09) Reverse CTCGAACCACATCCTTCTCT (SEQ NO: 10) Gene Specific Primers for Ccna2 (212 bp product) Forward GATAGATTCCTCTCCTCCATG (SEQ NO: 11) Reverse TCACACACTTAGTGTCTCTGG (SEQ NO: 12)

Example 1 Clinical and Embryology Data

Of all 1117 IVF treatments performed at Stanford University in 2005, 822 were fresh IVF cycles that used the patients' own oocytes (FIG. 1, panel A). Based on our exclusion criteria, 157 cycles were excluded for a variety of medical and non-medical reasons.

The 157 cycles that were excluded consisted of: cancelled oocyte retrieval due to poor ovarian stimulation (63 cycles), cancelled embryo transfer due to complete lack of embryo development (8 cycles), cancelled embryo transfer due to unexpected medical or non-medical reasons (35 cycles), cycles that were not treated with gonadotropins (3 cycles), missing outcomes (8 cycles), and women being ≧45 years of age based on age alone (29 cycles). In our study, 160 patients underwent subsequent repeat cycles after a previously failed attempt for a total of 368 cycles. Of these, 126 patients had 2 IVF cycles performed, 25 patients had 3 cycles, 6 patients had 4 cycles, 1 patient had 5 cycles and 2 patients had 6 cycles performed in the same year at the same institution. 511 cycles (76.8%) with Day 3 embryo transfer and 154 cycles (23.2%) with Day 5 transfer, or a total of 665 IVF cycles, fulfilled the inclusion and exclusion criteria for analyses.

Clinical and embryology data on the remaining 665 cycles that satisfied inclusion and exclusion criteria, and their 4144 embryos, respectively, were analyzed to test the hypothesis that cohort-specific variables predict IVF cycle outcomes (FIG. 1). Of those 4144 embryos, the number of blastomeres or cells on day 3 was recorded for 4002 embryos (96.6%). Overall, 38.8% had 8 cells, the developmentally appropriate cell number, while 18.2% of embryos had ≦4 cells, and 33.6% had 5-7 cells (FIG. 2).

Example 2 Prognostic Significance and Correlation of Variables

We systematically examined the association of each variable with IVF outcomes, and the correlation of each pair of variables. Pair-wise logistic regression tests confirmed many known prognostic variables, including female age, day 3 FSH, and the number of 8-cell embryos. However, in addition to these known prognostic variables, we observed that cohort-specific variables such as fertilization rate and the rate of cleavage arrest were also significantly associated with IVF cycle outcome (p<0.001; Table 3). In contrast, except for male factor infertility (p<0.05), none of the conventional clinical infertility diagnoses were significantly associated with IVF outcomes. Notably, despite a high degree of correlation between many variables and age or day 3 FSH level, which estimates ovarian aging, neither age nor day 3 FSH level was correlated to cohort-specific embryo parameters (Table 4). Collectively, these results suggest that determinants other than age-related mechanisms and clinical diagnoses impact cohort-specific embryo developmental competence.

TABLE 4 Correlation between each pair of variables Maximum Average grade Percentage of Percentage of Day 3 No. of Average of embryos No. of 8-cell embryos with ≦4 Age Gravidity FSH level oocytes grade transferred embryos stage embryos cells Age 1.00 0.19 0.13 −0.30 −0.01 0.12 −0.25 0.03 0.03 Gravidity 0.19 1.00 0.01 −0.06 −0.09 −0.03 −0.03 0.08 −0.03 Maximum Day 3 FSH level 0.13 0.01 1.00 −0.24 0.02 0.05 −0.20 −0.02 −0.03 No. of oocytes −0.30 −0.06 −0.24 1.00 −0.02 −0.25 0.86 0.06 −0.05 Average grade −0.01 −0.08 0.02 −0.02 1.00 0.84 0.02 −0.35 0.29 Average grade of embryos 0.12 −0.03 0.05 −0.25 0.84 1.00 −0.28 −0.34 0.28 transferred No. of embryos −0.25 −0.03 −0.20 0.86 0.02 −0.28 1.00 0.05 −0.08 Percentage of 8-cell stage 0.03 0.08 −0.02 0.06 −0.35 −0.34 0.05 1.00 −0.51 embryos Percentage of embryos with ≦4 0.03 −0.03 −0.03 −0.05 0.29 0.28 −0.08 −0.51 1.00 cells Average cell no. of embryos 0.03 0.11 0.02 0.06 −0.39 −0.36 0.05 0.61 −0.83 No. of embryos transferred 0.25 0.06 −0.03 0.13 0.04 0.09 0.14 −0.15 0.04 Percentage of transferred −0.20 0.03 −0.20 0.35 −0.24 −0.42 0.41 0.77 −0.41 embryos at the 8-cell stage Percentage of transferred 0.15 0.03 0.00 −0.21 0.20 0.31 −0.28 −0.41 0.87 embryos at the ≦4-cell stage Average cell no. of embryos −0.13 0.02 −0.05 0.27 −0.28 −0.41 0.35 0.50 −0.70 transferred Fertilization rate 0.03 0.03 0.04 −0.06 0.04 −0.10 0.35 −0.02 −0.12 No. of 8-cell embryos −0.17 0.06 −0.20 0.68 −0.20 −0.39 0.77 0.51 −0.32 No. of 8-cell embryos −0.02 0.09 −0.10 0.38 −0.17 −0.30 0.45 0.55 −0.35 transferred Percentage Percentage Average cell Average cell No. of of transferred of transferred no. of No. of No. of 8-cell no. of embryos embryos at embryos at the embryos Fertilization 8-cell embryos embryos transferred the 8-cell stage ≦4-cell stage transferred rate embryos transferred Age 0.03 0.25 −0.20 0.15 −0.13 0.03 −0.17 −0.02 Gravidity 0.11 0.06 0.03 0.03 0.02 0.03 0.06 0.09 Maximum Day 3 FSH level 0.02 −0.03 −0.12 0.00 −0.05 0.04 −0.20 −0.10 No. of oocytes 0.06 0.13 0.35 −0.21 0.27 −0.06 0.68 0.38 Average grade −0.39 0.04 −0.24 0.20 −0.28 0.04 −0.20 −0.17 Average grade of embryos −0.36 0.09 −0.42 0.31 −0.41 −0.10 −0.39 −0.29 transferred No. of embryos 0.05 0.14 0.41 −0.28 0.35 0.35 0.77 0.45 Percentage of 8-cell stage 0.61 −0.15 0.77 −0.41 0.50 −0.02 0.51 0.55 embryos Percentage of embryos with ≦4 −0.83 0.04 −0.41 0.87 −0.70 −0.12 −0.32 −0.35 cells Average cell no. of embryos 1.00 −0.03 0.45 −0.67 0.81 0.04 0.35 0.39 No. of embryos transferred −0.03 1.00 −0.22 0.02 −0.06 0.16 −0.03 0.39 Percentage of transferred 0.45 −0.22 1.00 −0.48 0.58 0.14 0.64 0.70 embryos at the 8-cell stage Percentage of transferred −0.67 0.02 −0.48 1.00 −0.80 −0.22 −0.34 −0.41 embryos at the ≦4-cell stage Average cell no. of embryos 0.81 −0.06 0.58 −0.80 1.00 0.20 0.44 0.48 transferred Fertilization rate 0.04 0.16 0.14 −0.22 0.20 1.00 0.24 0.19 No. of 8-cell embryos 0.35 −0.03 0.64 −0.34 0.44 0.24 1.00 0.59 No. of 8-cell embryos 0.39 0.39 0.70 −0.41 0.48 0.19 0.59 1.00 transferred

Example 3 Thresholds of Non-Redundant, Prognostic Variables Defining Human Embryo Cohort Phenotypes

Sequential Multiple Additive Regression Tree (MART®) and Classification and Regression Tree (CART) analyses of all 30 variables (listed in Table 3 and its legend) determined that IVF cycle outcomes were most accurately predicted at ˜70% by using only four non-redundant variables: total number of embryos, rate of cleavage arrest in an embryo cohort, the number of 8-cell embryos in a cohort, and day 3 FSH level. Remarkably, these four variables all describe the embryo cohort rather than individual embryos, and were more informative than age, clinical diagnoses, or any measures of the transferred embryos. Interestingly, the total number of embryos, day 3 FSH, and the number of 8-cell embryos depended on and thus captured the effects of many other variables. In contrast, the rate of cleavage arrest was independent of any of those known variables. (Details on MART® and CART analyses are reported in Table 5, and FIG. 3).

TABLE 3 Association of each variable with pregnancy outcome Variables Estimate* S.E. P-Value Patient Characteristics and Clinical Diagnoses^(†) Age −0.10 0.02 2.16E−007 Maximum Day 3 FSH level −0.08 0.03 1.70E−003 Gravidity 0.036 0.066 5.86E−001 Male Factor (infertility diagnosis) 0.50 0.24 3.71E−002 IVF Cycle Characteristics Microdose lupron (flare) protocol −1.14 0.24 2.53E−006 Antagonist protocol −0.74 0.19 9.98E−005 Performance of ICSI −0.15 0.16 3.47E−001 No. of oocytes 0.08 0.01 1.58E−009 Embryo Cohort Parameters Fertilization rate 1.24 0.36 5.37E−004 No. of embryos 0.14 0.02 2.67E−012 Average cell no. of embryos 0.29 0.06 6.34E−006 No. of 8-cell embryos 0.26 0.04 2.88E−012 Percentage of 8-cell embryos 0.76 0.28 5.75E−003 Cleavage arrest rate^(‡) −1.28 0.35 2.76E−004 Average grade of embryos −0.091 0.17 5.88E−001 Parameters of Transferred Embryos Day 5 embryo transfer^(§) 1.40 0.19 7.51E−013 No. of embryos transferred 0.0058 0.053 9.12E−001 Average cell no. of embryos transferred 0.47 0.07 2.19E−010 Percentage of transferred embryos at the 1.33 0.21 5.35E−010 8-cell stage No. of 8-cell embryos transferred 0.41 0.08 4.40E−008 No. of embryos with ≦4 cells −2.14 0.49 1.06E−005 transferred Average grade of embryos transferred −0.52 0.17 2.61E−003 *Positive and negative estimates indicate association with positive and negative pregnancy outcomes, respectively. ^(†)Clinical infertility diagnoses that were not significantly associated with pregnancy outcome (p-value > 0.05) were not listed: uterine factor, polycystic ovarian syndrome, endometriosis, tubal ligation, tubal disease, hydrosalpinges, unexplained infertility, and “other diagnoses”. Each IVF case may have more than one clinical infertility diagnosis. ^(‡)Cleavage arrest rate is defined as the percentage of embryos with 4 or fewer cells on Day 3 of in vitro culture. ^(§)Day 5 embryo transfer is arbitrarily listed under Parameters of Transferred Embryos. It can also be considered an Embryo Cohort Parameter, as it depends on the total number of embryos and the number of 8-cell embryos.

TABLE 5 Models generated by MART ® to identify non-redundant, prognostic variables Cross-validated Degree of Learning Tree (CV) Prediction Model Interaction Rate* Number^(†) Error Rate^(††) 1 2 0.0100 2 0.300800 2 3 0.0010 3 0.300800 8 20 0.0010 4 0.308300 6 10 0.0001 4 0.315800 3 4 0.1000 30 0.323300 4 5 0.0020 16 0.323300 5 6 0.0100 16 0.330800 7 15 0.0001 3 0.330800 *One of the “boosting” tuning parameters in MART ® to prevent “over-fitting” of the data² ^(†)Number of trees constructed by MART ® ^(††)10-fold cross validation error

Of the prognostic thresholds identified, the most robust phenotypes are A1 and A2, and B1 and B2 (Table 6). Number of embryos <6 or ≧6 is used by all 5 top CART models, defines all other phenotypes (B to F), and can be applied to all cases. Specifically, the phenotype defined by having fewer than 6 embryos, has an odds ratio of 3.9 for no pregnancy compared to cases with ≧6 embryos (95% Confidence Interval [CI], 2.8 to 5.5). Similarly, the next most robust phenotypes are defined by the number of embryos and cleavage arrest rate, such that for cases with ≧6 embryos, those with cleavage arrest rate >14.6% are 3.0 times more likely to result in no pregnancy than those with cleavage arrest rate ≦14.6% (95% CI, 1.9 to 4.9).

TABLE 6 Prognostic thresholds defining cohort-specific phenotypes 8-cell Applicable 95% Embryos Cleavage mbryo FSH Pregnancy- No Pregnancy Cases - No. No. Reference Odds Confidence (No.)* Arrest (%)* (No.)* (mIU/mL)* No. (%)† No. (%)‡ (%)§ Trees¶ Condition|| Ratio Interval (C.I.) A1** ≧6 177 (57.7)  130 (42.3)  307 (46.2) 5 A2 <6 92 (25.7) 266 (74.3)  358 (53.8) 5 A1 3.9 (2.8, 5.5) B1 ≧6 ≦14.6 112 (70.4)  47 (29.6) 159 (23.9) 4 B2 ≧6 >14.6 65 (43.9) 83 (56.1) 148 (22.3) 4 B1 3.0 (1.9, 4.9) B3 ≧6 14.6-52.8 62 (47.3) 69 (52.7) 131 (19.7) 1 B1 2.6 (1.6, 4.3) B4 ≧6 ≦52.8 174 (60.0)  116 (40.0)  290 (43.6) n/a B1 10.6 (3.2, 49.6) B5 ≧6 >52.8  3 (17.6) 14 (82.3) 17 (2.6) 1 B4 6.7 (2.1, 30.9) C1 ≧6 ≧2 157 (63.6)  90 (36.4) 247 (37.1) 1 C2 ≧6 <2 20 (33.3) 40 (66.7) 60 (9.2) 1 C1 3.5 (1.9, 6.4) D1 ≧6 >14.6 ≧2 51 (53.1) 45 (46.9)  96 (14.4) 1 D2 ≧6 >14.6 <2 14 (26.9) 38 (73.1) 52 (7.8) 1 D1 3.0 (1.5, 6.5) E1 ≧6 >14.6 ≧2 ≦4.6 14 (82.4)  3 (17.6) 17 (2.6) 1 E2 ≧6 >14.6 ≧2 >4.6 34 (46.9) 37 (53.1)  71 (12.2) 1 E1 4.8 (1.4, 23.4) *Cohort phenotypes defined by thresholds of non-redundant prognostic variables. Each set of conditions (A-E) use “AND” as the operator where more than one condition is listed. †No. of cases that satisfy the threshold conditions and have pregnancy outcome. This percentage is calculated by using the No. Applicable Cases as denominator. In general, conditions that discriminate between pregnancy and no pregnancy outcomes more highly are more robust and are expected to be more useful in both clinical management and translational research. ‡No. of cases that satisfy the threshold conditions and have no pregnancy outcome. This percentage is calculated by using the No. Applicable Cases as denominator. §The No. Applicable Cases is the total number of cases that satisfy the threshold conditions. This percentage is calculated by using the total number of cycles (665) as the denominator. In general, the larger the number of applicable cases, the more useful the set of conditions are for clinical management and counseling. However, for the purpose of translational research, conditions that define a smaller number of cases may have more specific correlates on a molecular level. ¶No. Trees shows the number of CART trees that utilize each set of conditions. There area total of 5 trees. (See Supplemental Results.) Increased utilization indicates “usefulness” or “robustness” of that particular set of conditions. ||Reference condition against which the Odds Ratio and 95% C.I. for having no pregnancy is calculated. **Conditions A-E are listed from most robust and “useful” to least “useful” based on: the number of trees that utilize each set of conditions, the number of applicable cases, and the odds ratio and 95% CI.

In contrast, the rest of the thresholds listed in Table 6 are used by only 1 CART model each, and is applicable to fewer cases. However, as some of those phenotypes describe very specific subset of cases and have odds ratios that are highly discriminatory, they may be extremely useful depending on the clinical or translational research context. For example, for cases with ≧6 embryos, having cleavage arrest rates of 14.6-52.8% and >52.8% increase the odds of no pregnancy by 2.6 (95% CI 1.6 to 4.3) and 10.6 (95% CI 3.2 to 49.6), respectively, when compared to cases with cleavage rates of ≦14.6%.

Example 3 Analyses by Mart® and Cart Models

To overcome the challenges presented by the highly interactive nature and potentially non-linear dependence amongst variables, and their multicollinearity, all 30 variables listed in Table 5 and its legend were analyzed by MART® to generate models that utilize non-redundant prognostic variables. Eight models were generated by MART® with increasing complexity of individual trees for boosting, while the learning rate was chosen to produce a minimum test error for the given complexity. Among them, the 3 top-ranking models had cross-validated (CV) prediction error rates of 0.301 to 0.308, which separated them well from the other five models, whose CV error rates ranged from 0.315 to 0.331 (Table 5). The third model, however, was based on very complex individual trees yet showed a larger CV error than the two preceding models; thus it was excluded from the analysis. The resulting two top models, consistent with characteristics of meaningful regression tree models, used very few trees and shared common features, such that the two models collectively used only 5 trees containing 5 variables, while some of the other models used up to 16 to 30 trees each.

These 5 non-redundant prognostic variables were: total number of embryos, the rate of cleavage arrest, the number of 8-cell embryos, day 3 FSH level, and the number of 8-cell embryos transferred. In each model, removal of each of the first four variables while keeping all other parameters constant, increased the error rate of the model, thus confirming their significant contribution. However, removal of the number of 8-cell embryos transferred, did not alter the error rate (data not shown), which suggested that this variable was less relevant than others.

24 models representing all possible combinations of these 5 variables were analyzed by CART to further define thresholds that have prognostic significance. The top 5 trees generated by CART had superior prediction scores (0.6828 to 0.6950) compared to the rest of the models (0.565 to 0.6700). As there were shared features, these top 5 tree models utilize mostly the same threshold conditions for 4 variables, while the variable, number of 8-cell embryos transferred, was not utilized by any of these top models. Therefore, IVF cycle outcomes could be most accurately predicted at ˜70% by using only four non-redundant variables that are more informative than age, clinical diagnoses, or any measures of the transferred embryos.

In order to understand which factors amongst patient characteristics, diagnoses, and IVF treatment characteristics, in turn determined these four non-redundant, cohort-specific prognostic variables, tree models were constructed by MART to represent the dependence of each of these four prognostic variables. The total number of embryos, day 3 FSH, and the number of 8-cell embryos depended on and thus captured the effects of many other variables (FIG. 3). In contrast, the rate of cleavage arrest was independent of any of those known variables.

Example 4 Morpholino Mediated Gene Knockout Study

Here, we provide proof-of-concept of the efficiency and specificity of MO-mediated gene knockdown by testing the procedure on the Ccna2 gene. We then report the novel role of Oct4 that was revealed by MO-mediated gene knockdown. Ccna2, the gene encoding cell cycle regulator cyclin A2, has been suggested as an important transcriptional regulator in embryonic genome activation (Hara K T, et al. (2005) Dev Biol 286, 102-113), a critical developmental milestone at the 1- to 2-cell stages for which few clear mechanisms or regulators have emerged. Consistent with the literature, MO-mediated Ccna2 knockdown decreased cyclin A2 protein expression. In addition, our results showed that cyclin A2 is required for development beyond the 2-cell stage (FIG. 4, panels A-C, FIG. 5, panels A-D, Tables 1 and 7). MOs block translation of transcripts by steric hindrance in an efficient and gene-specific manner, which has been well established in zebrafish and other model organisms (Gore A V, et al. (2005) Nature 438, 1030-1035; Imai et al., (2006). Science 312, 1183-1187; Sumanas S & Larson J D (2002) Brief Funct Genomic Proteomic 1, 239-256; Yamada L, et al. (2003) Development 130, 6485-6495). Most importantly, MOs mediate rapid knockdown of transcripts regardless of their maternal or embryonic origin, before activation of downstream genes can provide partial “rescue” of the phenotype. Unlike siRNAs, MOs function independently of endogenous pathways, so the MO-mediated translational block should not limit knockdown efficiency or interfere with the endogenous mRNA degradation machinery.

By combining MO-mediated gene knockdown with global gene expression profiling and single-embryo level quantitative RT-PCR (q-PCR), we determined the influence of Oct4 on gene expression, and analyzed the Oct4-regulated gene network in the early embryo (FIG. 6 and FIG. 7). Consistent with the literature, we confirmed Oct4 gene expression at the 1-cell stage (FIG. 8). After 1-cell embryos were microinjected with 0.6 mM Oct4-MO, the rate of developmental arrest at the 1- to multicell stages was dramatically higher than that observed for uninjected and mismatch (Oct4-MM) controls (FIG. 9, panels A and B). Of embryos injected with Oct4-MO that reached the multicell stage, 86.8±8.3% arrested and did not form morulae, compared to 10.5±10.5% embryos injected with Oct4-MM (p<0.01; data not shown). Most remarkably, none of the Oct4-MO-injected embryos developed to blastocysts, compared to relatively high blastocyst rates of Oct4-MM-injected and uninjected embryos (p<0.01; FIG. 9, panel C). Further, the specificity of Oct4-MO is supported by the direct relationship between the phenotype severity and presumed “gene-dosage” as titrated by Oct4-MO concentration (FIG. 9, panels D and E). Oct4 protein expression was indeed reduced in Oct4-MO-injected embryos at the 4-cell (FIG. 10) and multi-cell stages (FIG. 11, panel A, and FIG. 12). Injection of another MO, targeting an intron-exon boundary in Oct4, confirmed that disruption of Oct4 function is detrimental to development before the blastocyst stage (FIG. 13, panels A-C).

The critical function of Oct4 at the 1- to 2-cell transition was embryo-autonomous. The effects of Oct4 knockdown could not be rescued by media conditioned by uninjected embryos or the in vivo environment provided by transferring injected embryos to oviducts of appropriately timed surrogate mothers (data not shown). Co-injection of low (3.6 ng/μL) or high (3.6 ng/μL) concentrations of unaltered, full-length Oct4 mRNA with 0.6 mM Oct4-MO resulted in a decrease in the percentage of embryos arresting at the 1- to multicell stages, compared to co-injection of control mRNA encoding a modified enhanced yellow fluorescent protein (mEYFP) (FIG. 11, panel B). No embryos co-injected with Oct4 mRNA arrested at the multicell stage, while 80.0±5.2% arrested after co-injection of mEYFP mRNA (p<0.01; data not shown). Thus, co-injection of Oct4 mRNA, but not control mRNA, partially rescued the Oct4-MO-induced multicell stage arrest phenotype. The failure of achieving full rescue of the phenotype may be due to insufficient Oct4 expression after co-injection of Oct4 mRNA at the low concentration, inappropriately high Oct4 expression at the high concentration, or relative instability of the in vitro transcribed Oct4 mRNA compared to Oct4-MO; further, these possibilities are not mutually exclusive. Hence, we next tested whether Oct4 over-expression itself would interfere with development.

Injection of Oct4 mRNA resulted in over-expression as quantified by q-PCR, but did not cause ectopic expression of Oct4 protein (data not shown). Oct4 over-expression indeed induced developmental arrest in a dosage-dependent manner, while injection of comparable or greater amounts of mEYFP mRNA interfered minimally with blastocyst development (FIG. 11, panel C). The “gene dosage” effect of Oct4 RNA injection may be due to enhanced Oct4 functions in transcriptional regulation, or Oct4 over-production may allow non-specific promoter-binding, or extra Oct4 causes inappropriate sequestration and subsequent inactivation of co-factors. Collectively, these data definitively showed Oct4 expression was required, and that its correct level was critical to early embryo development, just as pluripotency of ESCs depends on a precise range of Oct4 expression levels (Stefanovic S & Puceat M (2007) Cell Cycle 6, 8-10).

TABLE 7 Summary of the Number of Embryos Tested and the Number of Experiments Performed for Each Condition No. No. Injected Uninjected No. Experiment Condition Embryos Embryos experiments Ccna2 knockdown Ccna2-MO 0.75 mM 94 65 8 Ccna2-MM 0.75 mM 75 101 9 Ccna2-MO Ccna2-MO 0.75 mM 26 28 3 Immunocytochemistry Ccna2 “gene dosage” Ccna2-MO, 0.5 mM 39 30 3 Ccna2-MO, 0.25 mM 50 29 3 Oct4 knockdown Oct4-MO, 0.60 mM 41 37 4 Oct4-MM, 0.60 mM 57 30 3 Oct4-MO, 0.40 mM 79 25 3 Oct4-MO, 0.20 mM 63 30 3 Oct4E4-MO, 0.60 mM 35 30 3 Oct4E4-MM, 0.60 mM 32 30 3 Oct4-MO Oct4-MO, 0.60 mM 32 22 3 Immunocytochemistry Oct4-MM, 0.60 mM 20 20 3 Rescue 0.036 μg/μl Oct4 mRNA + 32 30 3 0.60 mM Oct4-MO 0.036 μg/μl EYFP mRNA + 72 30 3 0.60 mM Oct4-MO Overexpression 0.09 μg/μl Oct4 mRNA 24 20 3 0.036 μg/μl Oct4 mRNA 33 25 3 3.6 ng/μl Oct4 mRNA 35 30 3 0.09 μg/μl EYFP mRNA 41 20 2 Oct4-MO/Conditioned Oct4-MO, 0.60 mM, 20 20 2 Media conditioned media 20 20 2 Oct4-MO, 0.60 mM, unconditioned media Ccna2-MO gene chip Ccna2-MO, 0.75 mM 60 60 3 Oct4-MO gene chip Oct4-MO, 0.6 mM 60 60 3 Oct4-MO single embryo Oct4-MO, 0.60 mM, 2-cell 14-20 14-20 3-5 QPCR stage Control-MO, 0.60 mM, 2-  5-10 n/a 2 cell stage

Example 5 Gene Regulation by Oct4

To dissect the mechanisms of Oct4 function, we compared the global gene expression profile of Oct4 knockdown embryos to the effects of Ccna2 knockdown and to uninjected controls at the mid-2-cell stage. The goal was to identify differential gene expression that coincides with the first major wave of embryonic genome activation at the mid-2-cell stage (Hamatani T, Carter M G, Sharov A A, & Ko M S (2004) Dev Cell 6, 117-1317; Wang Q T, et al. (2004) Dev Cell 6, 133-1448) (Tables 8, A and B, 9, A and B). Analysis by an unsupervised algorithm showed that the embryo samples clustered according to the experimental conditions, which further supported the specific and non-random effects of gene knockdown (FIG. 14, panel A). At an arbitrary threshold false detection rate (FDR) of 0.05, the Oct4-regulated gene set is five times larger compared to the number of genes changing expression in response to cyclin A2 knockdown (FIG. 14, panel B). The different sizes of the under-expressed versus over-expressed Oct4-knockdown gene sets suggest that Oct4 may be predominantly activating rather than repressing transcription (FIG. 14, panel B). Some of the Oct4 candidate target genes have previously been identified as putative Oct4 targets based on mESC chromatin immunoprecipitation (ChIP) data or genomic sequence analysis of Oct4-binding sites (Zhou Q, Chipperfield H, Melton D A, & Wong W H (2007) Proc Natl Acad Sci USA 104, 16438-16443) (Table 10).

The list of cyclin A2-regulated genes was rich in genes encoding factors for chromatin modification and remodelling (p=0.005), nucleotide metabolism (p=0.01), and chromosome organization (p=0.01; Tables 11 A and B). Oct4-regulated genes were significantly enriched for translation (p=1.1×10⁻⁴) and RNA processing functions (p=3.0×10⁻⁵) (Tables 11, C and D). Comparison of our data with published Oct4-regulated networks in mouse ESCs indicates that Oct4 has distinct and specific post-transcriptional and translational regulatory functions mediated by its control of genes encoding subunits in eukaryotic translation initiation factors (Eif), including Eif3c, and Eif3b. Interestingly, these two Eif subunits are evolutionarily conserved from yeast to human, and are amongst the six subunits comprising the functional core of mammalian Eif3, the largest of the Eif complexes (Masutani M, Sonenberg N, Yokoyama S, & Imataka H (2007) Embo J 26, 3373-3383). In addition to its embryo-specific function, Oct4 also controls the expression of genes encoding post-transcriptional regulators Dppa5 and Piwil2 (also known as Mili), as it does in ESCs (data not shown). Dppa5 is an embryo-, germ cell- and ESC-specific RNA-binding protein whose role in maternal-embryonic transition is not known. However, Piwil2 and its bound pi-RNAs, are known for their role in regulating retrotransposons in the fully-grown mouse oocyte (Watanabe T, et al. (2008) Nature 453, 539-543.26). Collectively, our data indicate that the Oct4 has a distinct, developmental stage-specific role in controlling genes encoding post-transcriptional regulators, in addition to its conserved functions shared amongst pluripotent cell types.

Table 8A: Genes That Have Higher Expression Levels In Oct4-MO-Injected Compared To Uninjected Embryos (Following the Examples Section) Table 8B: Genes That Have Lower Expression Levels In Oct4-MO-Injected Compared To Uninjected Embryos (Following the Examples Section) Table 9A: Genes That Have Higher Expression Levels In Ccna2-MO-Injected Compared To Uninjected Embryos (Following the Examples Section Table 9B: Genes That Have Lower Expression Levels In Ccna2-MO-Injected Compared To Uninjected Embryos (Following the Examples Section)

TABLE 10 Oct4 Candidate Target Genes That Have Putative Oct4 Binding Sites Based on Genomic Sequence Analysis or Mouse ESC Chromatin Precipitation (ChIP) Data Downregulated in Oct4 knockdown embryos: 1700021F05Rik: RIKEN cDNA 1700021F05 gene 2900073H19Rik: RIKEN cDNA 2900073H19 gene Arhgap8: Rho GTPase activating protein 8 Cbfa2t2h: core-binding factor, runt domain, alpha subunit 2, translocated to, 2 homolog (human) Cdt1: chromatin licensing and DNA replication factor 1 Dido1: death inducer-obliterator 1 Dpm1: dolichol-phosphate (beta-D) mannosyltransferase 1 Dppa5: developmental pluripotency associated 5 Eif4e2: eukaryotic translation initiation factor 4E member 2 Elovl6: ELOVL family member 6, elongation of long chain fatty acids (yeast) Etv5: ets variant gene 5 Fkbp4: FK506 binding protein 4 Gnb2l1: guanine nucleotide binding protein (G protein), beta polypeptide 2 like 1 Hexb: hexosaminidase B Igf2bp1: insulin-like growth factor 2 mRNA binding protein 1 Klf9: Kruppel-like factor 9 Mkrn1: makorin, ring finger protein, 1 Mtf2: metal response element binding transcription factor 2 Myg1: melanocyte proliferating gene 1 Pa2g4: proliferation-associated 2G4 Pitpnc1: phosphatidylinositol transfer protein, cytoplasmic 1 Ppm1a: protein phosphatase 1A, magnesium dependent, alpha isoform Rest: RE1-silencing transcription factor Rif1 /// LOC671598: Rap1 interacting factor 1 homolog (yeast) /// similar to Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) (mRif1) Slc19a3: solute carrier family 19 (sodium/hydrogen exchanger), member 3 Slc22a12: solute carrier family 22 (organic anion/cation transporter), member 12 Slc25a36: solute carrier family 25, member 36 Tfrc: transferrin receptor Tnpo3: transportin 3 Ube2h: ubiquitin-conjugating enzyme E2H Ube2o: ubiquitin-conjugating enzyme E2O Zfp297b: zinc finger protein 297B Upregulated in Oct4 knockdown embryos BC022623: cDNA sequence BC022623 2810429O05Rik: RIKEN cDNA 2810429O05 gene Blcap: bladder cancer associated protein homolog (human) Icosl: icos ligand Sox2: SRY-box containing gene 2 Bcas2: breast carcinoma amplified sequence 2 Ldlr: low density lipoprotein receptor Zfp219: zinc finger protein 219 Arl4c /// LOC632433: ADP-ribosylation factor-like 4C /// similar to ADP-ribosylation factor-like protein 7 Tcl1: T-cell lymphoma breakpoint 1 Dcp1a: decapping enzyme Nes: nestin Rbpsuh: Recombining binding protein suppressor of hairless (Drosophila)

TABLE 11A Functional Categories That Were Enriched In Downregulated Genes In The Ccna2 Knockdown Model GOBPID P-value Term GO: 0050875 1.1E−3 cellular physiological process** GO: 0016568 4.0E−3 chromatin modification* GO: 0042254 4.0E−3 ribosome biogenesis and assembly** GO: 0006338 4.8E−3 chromatin remodeling* GO: 0007028 0.01 cytoplasm organization and biogenesis** GO: 0044237 0.01 cellular metabolism** GO: 0007582 0.01 physiological process GO: 0006139 0.01 nucleobase, nucleoside, nucleotide and nucleic acid metabolism* GO: 0008152 0.01 metabolism GO: 0006376 0.01 mRNA splice site selection* GO: 0006413 0.01 translational initiation** GO: 0007001 0.01 chromosome organization and biogenesis (sensu Eukaryota)* GO: 0007001 GO: 0007001 GO: 0006996 0.01 organelle organization and biogenesis* GO: 0007046 0.01 ribosome biogenesis** GO: 0043170 0.02 macromolecule metabolism** GO: 0051276 0.02 chromosome organization and biogenesis GO: 0006325 0.02 establishment and/or maintenance of chromatin architecture GO: 0006323 0.02 DNA packaging* GO: 0016043 0.02 cell organization and biogenesis GO: 0044238 0.03 primary metabolism** GO: 0000245 0.03 spliceosome assembly GO: 0006486 0.03 protein amino acid glycosylation GO: 0009059 0.03 macromolecule biosynthesis** GO: 0043413 0.03 biopolymer glycosylation GO: 0009101 0.04 glycoprotein biosynthesis GO: 0006364 0.04 rRNA processing GO: 0006412 0.04 protein biosynthesis** GO: 0006259 0.04 DNA metabolism GO: 0016072 0.04 rRNA metabolism** GO: 0009100 0.05 glycoprotein metabolism Notes: **Indicates the categories that were enriched in the Oct4 data set as well. *indicates functional categories that were specifically enriched in Ccna2 knockdown.

TABLE 11B Functional Categories That Were Enriched In Upregulated Genes In The Ccna2 Knockdown Model GOBPID P-value Term GO: 0044262 7.1E−4 cellular carbohydrate metabolism

TABLE 11C Functional Categories That Were Enriched In Downregulated Genes In The Oct4 Knockdown Model GOBPID P-value Term GO: 0006412 1.8E−7 protein biosynthesis** GO: 0009059 1.3E−6 macromolecule biosynthesis** GO: 0006413 3.6E−6 translational initiation** GO: 0009058 1.8E−5 biosynthesis GO: 0044249 2.1E−5 cellular biosynthesis GO: 0042254 2.3E−5 ribosome biogenesis and assembly** GO: 0006396 3.0E−5 RNA processing* GO: 0007046 3.3E−5 ribosome biogenesis** GO: 0016070 3.9E−5 RNA metabolism** GO: 0007028 7.0E−5 cytoplasm organization and biogenesis** GO: 0043037 1.1E−4 Translation* GO: 0043170 1.2E−4 macromolecule metabolism** GO: 0019538 1.6E−4 protein metabolism GO: 0044238 3.1E−4 primary metabolism** GO: 0044267 3.1E−4 cellular protein metabolism GO: 0050875 3.3E−4 cellular physiological process** GO: 0044237 5.3E−4 cellular metabolism** GO: 0044260 5.7E−4 cellular macromolecule metabolism Note: **Indicates categories that were enriched in the Ccna2 data set as well. *indicates functional categories that were specifically enriched in Oct4 knockdown.

TABLE 11D Functional Categories That Were Enriched In Upregulated Genes In The Oct4 Knockdown Model GOBPID P-value Term GO: 0044262 2.0E−4 Alcohol metabolism

Example 6 OCT4 Function at the 1- to 2-Cell Stage

In order to understand the role of Oct4 in reprogramming the early embryo, we examined its role in embryonic genome activation and maternal transcript degradation. Overall, Oct4 regulates gene expression pertinent to basic machinery required for the entire spectrum of gene regulation, including transcription involving all three RNA polymerases, translation, RNA processing such as regulation of polyadenylation, and mRNA degradation proteins (Table 12). High levels of mRNA from developmental genes, such as Six1, Nestin, and Hoxa3, indicated that Oct4 was required for their repression, while excessive levels of maternal transcripts that would normally be rapidly degraded, such as Zar1 and Nobox1, indicated that Oct4 knockdown interfered with the mRNA degradation machinery. Thus, Oct4 has developmental stage- and cell-specific functions, and has an important role in the processes that mark maternal-embryonic transition.

To further define the Oct4-regulated gene network, we selected 42 genes representing transcriptional, post-transcriptional and signaling functions for q-PCR assays. We analyzed RNA from single Oct4-MO-injected and control embryos and focused on genes that were under-expressed in Oct4 knockdown. After removing data related to 3 genes for which there were technical difficulties, expression changes of 39 genes were appropriately measured based on analysis using a linear model (See Methods and Materials). Of those, 34 or ˜87% showed altered expression levels in Oct4 knockdown in the expected directions (FIG. 14, panel C and FIG. 15), while 5 genes, including Sox2, did not change (data not shown). 21 of the 34 genes, or ˜62%, showed statistically significant differential expression by q-PCR at p<0.05 or less, while injection of a control MO did not alter expression of any of the genes assayed (data not shown). Thus, we have proven that Oct4 directly or indirectly regulates genes encoding the entire spectrum of transcriptional and post-transcriptional regulators at the 1- to 2-cell stages.

Our single-embryo data allowed us to go beyond simply validating our gene chip data. Methods using samples comprised of pooled cells or embryos, generate relative gene expression that represents an average of all cells assayed, but they cannot discern between genes that are consistently differentially regulated versus those with a tendency towards stochastic changes; similarly, rare outlier embryos expressing unique transcriptomes are not recognized (Bengtsson M, Stahlberg A, Rorsman P, & Kubista M (2005) Genome Res 15, 1388-1392; Chang H H, et al. (2008) Nature 453, 544-547; Warren L, Bryder D, Weissman I L, & Quake S R (2006) Proc Natl Acad Sci USA 103, 17807-17812). By analyzing quantitative expression data at the single-embryo level, we were able to make this discrimination. We presume genes whose relative expression is consistent amongst single embryos have a higher likelihood to be essential nodes in a gene regulatory network, which is expected to respond to perturbations in a consistent and predictable manner. The gene set was restricted to genes whose differential expression (represented by the difference in threshold cycles, ΔC_(T)) ΔC_(T) is greater than expression differences amongst single embryos (represented by standard error of the mean, s.e.m.). We propose a hierarchy in the Oct4-regulated gene network in which 29 genes are ordered based on their increasing s.e.m., or inter-embryo variation and presumed decreasing biological significance in this network (FIG. 16, panel A). Taken together, we have identified and ranked potential key nodes of this network in a quantitative fashion.

The data shows that in the unique developmental context of maternal-embryonic transition, concomitant with massive mRNA degradation and dramatic reprogramming, Oct4 controls the expression of many transcriptional regulators. Oct4 also maintains the expression of many genes, such as Eif3c, Papola, Piwil2, Eif3b, Eif4e, Rbm3 and Cpsf4, that are involved in the post-transcriptional control. Through its influence on both the transcriptional and post-transcriptional regulators, Oct4 can directly or indirectly affect many essential processes, such as chromatin remodelling, epigenetic regulation, apoptosis, cell cycle regulation, and signalling, during early developmental program (FIG. 16, panel B).

TABLE 12 Candidate Oct4-Regulated Genes That Function In Transcription, Translation, RNA Processing, Chromatin Remodeling, Signaling, Apoptosis And The Cell Cycle. False Gene Fold detection T. P- Symbol change rate (FDR) value POL I transcription upstream binding transcription factor, RNA polymerase I Ubtf 0.49 0.02667 0.00424 arginyl-tRNA synthetase Rars 0.47 0.03200 0.00131 POL II transcription BTAF1 RNA polymerase II, B-TFIID transcription factor- Btaf1 0.12 0.03834 0.00833 associated, (Mot1 homolog, S. cerevisiae) mediator of RNA polymerase II transcription, subunit 8 Med8 0.25 0.03405 0.00142 homolog (yeast) transcription elongation factor B (SIII), polypeptide 3 Tceb3 0.29 0.01471 0.00001 TAF9 RNA polymerase II, TATA box binding protein Taf9 0.30 0.02151 0.00027 (TBP)-associated factor polymerase (RNA) II (DNA directed) polypeptide H Polr2h 0.42 0.02586 0.00859 elongation factor RNA polymerase II 2 Ell2 0.49 0.03696 0.00098 cofactor required for Sp1 transcriptional activation, subunit 2 Med14 0.50 0.03794 0.00156 POL III transcription general transcription factor IIIC, polypeptide 4 Gtf3c4 0.07 0.00000 0.00002 general transcription factor IIIC, polypeptide 5 Gtf3c5 0.34 0.03209 0.00212 BRF2, subunit of RNA polymerase III transcription Brf2 0.34 0.04385 0.05104 initiation factor, BRF1-like general transcription factor IIIC, polypeptide 2, beta Gtf3c2 0.35 0.03314 0.00047 general transcription factor III C 1 Gtf3c1 0.47 0.03303 0.00236 polymerase (RNA) III (DNA directed) polypeptide A Polr3a 0.55 0.04421 0.01694 polymerase (RNA) III (DNA directed) polypeptide E Polr3e 0.56 0.03366 0.00134 Translational control, RNA processing, and posttranscriptional regulation Translational initiation eukaryotic translation initiation factor 2C, 5 Eif2c5 0.09 0.01370 0.00022 eukaryotic translation initiation factor 5B Eif5b 0.14 0.03802 0.00002 eukaryotic translation initiation factor 3, subunit 9 (eta) Eif3b 0.29 0.03803 0.00358 eukaryotic translation initiation factor 3, subunit 8 Eif3c 0.36 0.00000 0.00016 eukaryotic translation initiation factor 3, subunit 3 (gamma) Eif3h 0.42 0.03226 0.00485 eukaryotic translation initiation factor 3, subunit 4 (delta) Eif3g 0.47 0.04924 0.01507 integrin beta 4 binding protein Eif6 0.53 0.02756 0.00236 eukaryotic translation initiation factor 4, gamma 1 Eif4g1 0.59 0.04065 0.00041 eukaryotic translation initiation factor 2, subunit 1 alpha Eif2s1 0.60 0.04879 0.00311 eukaryotic translation initiation factor 4E /// hypothetical Eif4e 0.65 0.03742 0.00177 LOC630527 eukaryotic translation initiation factor 3, subunit 10 (theta) Eif3s10 0.66 0.04070 0.01798 Translational repression piwi-like homolog 2 (Drosophila) Piwil2 0.34 0.02778 0.00051 eukaryotic translation initiation factor 4E member 2 Eif4e2 0.46 0.02553 0.01084 3′ end processing poly (A) polymerase alpha Papola 0.10 0.02475 0.00014 cleavage and polyadenylation specific factor 6 Cpsf6 0.20 0.03256 0.00009 cleavage and polyadenylation specific factor 4 Cpsf4 0.48 0.03542 0.00233 Translational termination eukaryotic translation termination factor 1 Etf1 0.36 0.02717 0.00207 Nonsense mediated decay (NMD) eukaryotic translation initiation factor 3, subunit 6 Eif3e 0.21 0.00000 0.00000 Other RNA binding and processing integrator complex subunit 7 Ints7 0.10 0.02757 0.00004 RNA binding motif protein 3 Rbm3 0.20 0.03791 0.00037 RNA binding motif protein 4 Rbm4 0.42 0.04967 0.00236 developmental pluripotency associated 5 Dppa5 0.46 0.03672 0.00786 RNA binding motif protein 5 Rbm5 0.52 0.03415 0.00245 proliferation-associated 2G4 Pa2g4 0.70 0.04956 0.01729 Pre-mRNA processing and transport Heterogeneous nuclear ribonucleoprotein U 0.18 0.03688 0.00020 PRP4 pre-mRNA processing factor 4 homolog (yeast) Prpf4 0.34 0.03828 0.00128 RNA, U transporter 1 Snupn 0.35 0.01681 0.00227 PRP38 pre-mRNA processing factor 38 (yeast) domain Prpf38b 0.48 0.04103 0.00548 containing B protein phosphatase 1G (formerly 2C), magnesium- Ppm1g 0.48 0.02463 0.00012 dependent, gamma isoform heterogeneous nuclear ribonucleoprotein A/B Hnrpab 0.58 0.03233 0.00100 heterogeneous nuclear ribonucleoprotein A1 Hnrpa1 0.63 0.04981 0.00961 heterogeneous nuclear ribonucleoprotein K Hnrpk 0.64 0.04473 0.01239 heterogeneous nuclear ribonucleoprotein M Hnrpm 0.63 0.04884 0.00724 Transcriptional regulation homeodomain interacting protein kinase 3 Hipk3 0.17 0.04003 0.00031 Kruppel-like factor 9 Klf9 0.17 0.00000 0.00020 nuclear respiratory factor 1 Nrf1 0.20 0.01923 0.00073 integrator complex subunit 4 Ints4 0.34 0.03520 0.00080 homeodomain interacting protein kinase 1 Hipk1 0.35 0.01786 0.00073 Pbx/knotted 1 homeobox Pknox1 0.37 0.03796 0.00484 proline, glutamic acid and leucine rich protein 1 Pelp1 0.40 0.02415 0.00573 core-binding factor, runt domain, alpha subunit 2, 0.41 0.04076 0.02903 translocated to, 2 homolog (human) YY1 transcription factor Yy1 0.43 0.03853 0.00074 GATA binding protein 4 Gata4 0.45 0.03963 0.00325 metastasis-associated gene family, member 2 Mta2 0.51 0.03395 0.00326 BCL2-associated transcription factor 1 Bclaf1 0.54 0.02664 0.00242 RE1-silencing transcription factor Rest 0.62 0.03827 0.00983 ets variant gene 5 Etv5 0.50 0.04900 0.00576 makorin, ring finger protein, 1 Mkrn1 0.58 0.03793 0.00310 Chromatin remodeling, epigenetic regulation jumonji domain containing 1B Kdm3b 0.14 0.03770 0.00132 jumonji, AT rich interactive domain 1C (Rbp2 like) Kdm5c 0.23 0.01408 0.00075 sirtuin 1 ((silent mating type information regulation 2, Sirt1 0.28 0.01136 0.00002 homolog) 1 (S. cerevisiae) methyltransferase like 2 Mettl2 0.37 0.03333 0.00010 jumonji domain containing 1A Kdm3a 0.38 0.04874 0.00764 SWI/SNF related, matrix associated, actin dependent Rsc8 0.41 0.03665 0.01049 regulator of chromatin, subfamily c, member 1 jumonji, AT rich interactive domain 1B (Rbp2 like) Kdm5b 0.57 0.03738 0.00388 eukaryotic translation initiation factor 2, subunit 3, structural gene X-linked /// similar to eukaryotic translation 0.57 0.04905 0.00183 initiation factor 2, subunit 3, structural gene X-linked Histone H3-specific HAT activity general transcription factor IIIC, polypeptide 4 Gtf3c4 0.07 0.00000 0.00002 general transcription factor IIIC, polypeptide 5 Gtf3c5 0.34 0.03209 0.00212 GCN5 general control of amino acid synthesis-like 2 (yeast) Gcn5 0.34 0.02525 0.00159 general transcription factor IIIC, polypeptide 2, beta Gtf3c2 0.35 0.03314 0.00047 general transcription factor III C 1 Gtf3c1 0.47 0.03303 0.00236 H3 histone, family 3A H3f3a 0.53 0.04006 0.00865 Signaling pathways (Fgf4, Bmp, Toll, Egf, Mapk, Erk, Igf2, Amp) fibroblast growth factor 4 Fgf4 0.09 0.02591 0.00088 signaling intermediate in Toll pathway-evolutionarily Ecsit 0.17 0.01935 0.00000 conserved protein kinase, AMP-activated, gamma 1 non-catalytic Prkag1 0.19 0.03786 0.00010 subunit insulin-like growth factor 2 mRNA binding protein 1 Imp1 0.26 0.04930 0.00047 bone morphogenetic protein receptor, type 1A Bmpr1a 0.35 0.02347 0.00005 fibroblast growth factor receptor-like 1 Fgfrl1 0.34 0.03349 0.01815 interleukin 17 receptor D Il17rd 0.35 0.01961 0.00052 mitogen activated protein kinase 1 Mapk1 0.39 0.04889 0.00710 splicing factor, arginine/serine-rich 15 /// similar to splicing Sfrs15 0.47 0.02113 0.00047 factor, arginine/serine-rich 15 protein phosphatase 1A, magnesium dependent, alpha Ppm1a 0.46 0.02525 0.00280 isoform protein kinase C, delta Prkcd 0.45 0.03465 0.02184 insulin-like growth factor 2 receptor Igf2r 0.53 0.04738 0.00600 Apoptosis junction-mediating and regulatory protein Jmy 0.21 0.00000 0.00036 sphingosine-1-phosphate phosphatase 1 Sgpp1 0.23 0.01538 0.00160 cathepsin B Ctsb 0.28 0.00000 0.00024 death inducer-obliterator 1 Dido1 0.46 0.03440 0.00196 Cell cycle, DNA replication, DNA repair, cell division, chromosome segregation, cell growth, cell size origin recognition complex, subunit 4-like (S. cerevisiae) Orc41 0.17 0.01852 0.00383 purine rich element binding protein B Purb 0.29 0.02669 0.00019 chromosome segregation 1-like (S. cerevisiae) Cse1l 0.34 0.03254 0.00002 minichromosome maintenance deficient 5, cell division Mcm5 0.34 0.01852 0.00004 cycle 46 (S. cerevisiae) kinesin family member 11 Kif11 0.34 0.01938 0.00170 replication factor C (activator 1) 2 Rfc3 0.40 0.04420 0.00919 kinesin family member 22 Kif22 0.42 0.02667 0.00033 protein phosphatase 2 (formerly 2A), catalytic subunit, beta Ppp2cb 0.43 0.03243 0.00658 isoform centromere protein E Cenpe 0.54 0.03801 0.00299 Rap1 interacting factor 1 homolog (yeast) /// similar to mRif1 0.63 0.04515 0.00228 Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) (mRif1)

Example 6 Determination of Probability of Live Birth Event

In the US, 7.3 million couples suffer from clinical infertility, for which more than ˜120,000 IVF treatment cycles are performed per year. IVF is the most effective treatment for many infertility couples, but it is largely empiric, and may not result in a live birth for some couples despite multiple attempts. IVF treatment has revolutionized how physicians can help subfertile patients, but success rates with the use of autologous oocytes appear to have reached a plateau in the past decade. At an average cost of $12,000 per cycle, IVF treatment alone costs health care payers, most of whom are the couples themselves, more than $1 billion per year. However, the decision-making process for IVF can be daunting because IVF counseling and management decisions are often made based on the woman's chronological age, with non-standardized ways to adjust for various estimates of ovarian reserve and embryo quality. Further, quality of care is thought to vary amongst IVF clinics, but head-to-head comparisons are not possible in the absence of scientifically and rigorously defined prognostic stratification of patients. For a treatment that is physically, emotionally, and financially demanding, patients may feel that they are rolling the dice when deciding on whether to start or repeat IVF treatment. Consequently, there may be incongruence in patient- or self-selection for IVF, such that some patients with truly poor prognosis may develop unrealistic expectations, while others with truly good prognosis may miss opportunities for effective treatment. Although numerous publications have reported variables, including chronological age of the female patient, that are significantly associated with IVF outcomes, their contribution relative to outcomes is not clear, and we are even less certain how to directly apply those findings to counsel patients.

Accordingly, in the example we applied MART to analyze dichotomous live birth outcomes of a larger, four-year data set on 3338 fresh, non-oocyte donor IVF cycles and their associated embryos, including subsequent transfer of cryopreserved embryos from 2003 to 2006. Importantly, 57 variables pertaining to clinical diagnoses, treatment response, and embryo developmental parameters from 1,879 fresh, first-cycles were used to generate prediction models in an unbiased manner, with no pre-selection of variables based on previous literature. We identified four prognostic factors—the percentage of blastocysts (Blast Rate), total number of embryos (Embryo Number), total amount of gonadotropins required (TG), and endometrial thickness (EndoTh)—that determine live birth outcomes. The prognostic contribution of other variables, such as age and the number of 8-cell stage embryos on day 3, were optional once these four prognostic variables were known. Finally, the results show how our approach and findings can be applied to immediately improve patient counseling and management protocols, and how these rigorously defined prognostic criteria can fuel our concerted effort to improve quality assurance and decrease rates of multiple gestation.

Between Jan. 1, 2003 to Dec. 31, 2006, 5037 IVF treatments were performed in total, with annual volumes that were comparable across years. Of those, 3347 were fresh IVF cycles that used the patients' own oocytes and that fulfilled inclusion criteria. After applying exclusion criteria, 3338 cycles remained, of which 1879 were first-IVF cycles (C1), 778 were second-IVF cycles performed for patients who did not have live birth outcomes in C1 and who returned for their second treatment (C2); 312 were third-IVF cycles (C3); 369 cycles were fourth, fifth and sixth cycles, which were not analyzed (FIG. 17 and FIG. 18).

Data from C1, C2, and C3 were subsequently analyzed separately. Overall, 41% % of embryos had 8 blastomeres, the developmentally appropriate cell number, while 17% % of embryos had ≦4 cells, and 33% % had 5-7 cells, and 9% % had more than 8 cells (FIG. 19). This profile of in vitro human embryo development in IVF was consistent with previous reports. Further, the number of blastomeres formed by 10,687, 3,932 and 1,573 embryos by Day 3 of in vitro culture in C1, C2, and C3, were not significantly different, which suggested that embryo development was comparable amongst the first three cycles (p=0.6; FIG. 19).

We used C1 data only to generate our prediction models, because patients dropped out for a variety of reasons for which there were no controls (FIG. 18), and we did not want significant prognostic factors to be masked by cycle number; we did not know whether the drop out rates were comparable amongst patient subsets that varied in their prognoses. Consistent with other reports, a significant number of patients who had no live births dropped out after each unsuccessful cycle, and did not return for subsequent treatments. Nonetheless, C2 and C3 data were used to test whether the prediction models held true for subsequent treatments.

Variables Associated with Live Birth Outcomes

We first focused on 1879 C1 cycles and their associated 10,687 embryos that satisfied all inclusion and exclusion criteria. We systematically examined the association of each of 57 variables with live birth outcomes. These variables were chosen based on the quality and completeness of data entry, rather than prior scientific or clinical knowledge. Pair-wise logistic regression confirmed significant association of many variables with live birth outcomes, including patient's age, male partner's age, Day 3 FSH, and the number of prior clinical pregnancy losses (p<0.05) (Table 13). As expected, diminished ovarian reserve (DOR), a clinical diagnosis based on poor ovarian response in previous non-IVF infertility treatments or clomid challenge test, was highly negatively associated with live birth outcomes (p<0.0001), while the diagnosis of polycystic ovarian syndrome, which tends to increase ovarian response, was positively associated with live births (p<0.0001).

TABLE 13 Variables and their association with IVF live birth outcomes. Table 13A Continuous Variables Variables Estimate¹ S.E. p-value Mean⁵ StDev Pre-IVF Age of patient −1.27E−01 1.24E−02 4.12E−24 40.99 4.56 Age of male partner −6.31E−02 1.02E−02 2.28E−09 42.95 5.82 Body mass index −4.55E−03 6.17E−03 5.55E−01 24.90 9.75 No. of previous pregnancies² −1.16E−01 4.29E−02 1.07E−02 1.04 1.33 No. of previous term deliveries³ −3.05E−02 9.05E−02 7.49E−01 0.27 0.60 Spontaneous miscarriages⁴ −2.01E−01 7.36E−02 1.04E−02 0.41 0.82 Serum d.3 FSH (IU/L) −6.93E−02 1.60E−02 2.89E−05 8.05 4.92 Year 2.24E−02 4.73E−02 6.83E−01 4.32 1.12 Pre-OR Total amount of recombinant FSH (IU/L) −4.46E−04 3.94E−05 1.15E−28 3,512.03 1,587.94 Total amount of human menopausal −1.01E−03 1.18E−04 4.69E−17 1,257.11 544.11 gonadotropins (IU/L) Total amount of gonadotropin −3.55E−04 3.14E−05 1.36E−28 4,769.14 1,990.39 Endometrial Thickness (mm) 2.22E−01 2.66E−02 2.94E−16 10.00 2.10 No. of sperm motile after wash (million/mL) −3.92E−04 2.92E−04 2.53E−01 128.41 244.60 No. of sperm motile before wash (million/mL) −2.71E−04 3.39E−04 5.22E−01 106.46 198.93 Post-IVF Total no. of oocytes 1.06E−01 8.66E−03 2.53E−33 10.24 6.63 Percentage of normal and mature oocytes 3.36E+00 5.86E−01 2.69E−08 0.80 0.38 Normal fertilization (%) 1.32E+00 2.40E−01 9.74E−08 0.65 0.24 Unfertilized eggs (%) −1.08E+00 2.48E−01 2.79E−05 0.27 0.23 Abnormally fertilized eggs (%) −9.87E−01 4.34E−01 3.56E−02 0.08 0.14 Total number of embryos 1.78E−01 1.21E−02 2.43E−47 5.92 4.94 Blastocyst development (%) 3.05E+00 2.41E−01 3.03E−35 0.15 0.23 Compaction on day 3 2.66E−01 2.76E−01 4.51E−01 0.09 0.19 Average no. of cells per embryos 2.90E−01 4.57E−02 7.05E−10 6.76 1.32 No. embryos arrested at? 4 cells −1.32E−02 2.74E−03 3.00E−06 16.69 23.44 No. of 8-cell embryos 2.59E−01 2.25E−02 1.71E−29 2.73 2.74 Percentage of 8 cell embryos (%) 9.40E−03 1.89E−03 1.50E−06 40.49 29.09 No. of embryos cryopreserved 3.23E+00 2.88E−01 2.33E−28 0.11 0.19 Average grade of embryos −1.49E−01 1.11E−01 2.53E−01 1.83 0.61 Total no. of transferred embryos 9.59E−02 3.51E−02 1.04E−02 2.28 1.49 Average no. of cells per transferred embryos 5.37E−01 6.02E−02 2.07E−18 7.41 1.24 Average grade of transferred embryos −6.33E−01 1.24E−01 8.24E−07 1.62 0.62 No. of transferred embryos arrested with ? 4 −2.36E−02 3.29E−03 7.12E−13 8.56 24.50 cells No. of 8 cell embryos transferred 3.26E−01 5.43E−02 5.59E−09 1.47 1.07 Percentage of 8 cell embryos transferred 1.67E−02 1.62E−03 3.65E−24 59.61 39.12 Table 13B Categorical Variables Variables Estimate S.E. p-value Mean⁶ StDev Pre-IVF Diminished ovarian reserve −1.07E+00 1.23E−01 1.40E−17 0.39 0.49 Polycystic ovarian syndrome 7.58E−01 1.66E−01 1.01E−05 0.09 0.29 Unexplained female infertility 5.74E−01 1.70E−01 1.37E−03 0.09 0.28 Other causes for infertility −2.52E−01 1.14E−01 4.19E−02 0.34 0.47 Tubal disease −9.40E−02 1.66E−01 6.24E−01 0.12 0.32 Uterine Fibroids −1.87E−01 1.95E−01 4.51E−01 0.09 0.28 Endometriosis −9.18E−02 1.53E−01 6.23E−01 0.14 0.35 Male infertility 4.51E−02 1.07E−01 7.09E−01 0.42 0.49 Tubal Ligation 4.09E−02 3.72E−01 9.12E−01 0.02 0.14 Hydrosalpinx −7.22E−02 2.97E−01 8.08E−01 NA NA Season: summer 9.88E−02 1.54E−01 6.15E−01 0.22 0.42 Season: winter 1.32E−01 1.42E−01 4.63E−01 0.30 0.46 Season: fall 3.27E−01 1.54E−01 5.05E−02 0.20 0.40 Pre-OR Oral contraception 7.33E−01 1.85E−01 1.39E−04 0.87 0.34 Sperm collected surgically 1.57E−01 2.57E−01 6.23E−01 0.04 0.20 Sperm collection from frozen 2.61E−01 3.21E−01 5.22E−01 0.03 0.16 Sperm from donor −4.03E−01 4.56E−01 4.84E−01 0.02 0.13 Post-IVF Assisted Hatching −8.58E−01 1.26E−01 4.03E−11 0.33 0.47 Day 5 Embryo transfer 1.42E+00 1.20E−01 6.89E−31 0.27 0.44 Antagonist protocol −1.35E+00 1.21E−01 6.30E−28 0.47 0.50 Flare protocol −1.70E+00 1.84E−01 8.98E−20 0.18 0.39 Echotip catheter 6.83E−01 1.47E−01 7.64E−06 0.14 0.35 Other catheter −2.69E−01 4.67E−01 6.24E−01 0.02 0.13 Performance of ICS1 3.34E−01 1.07E−01 3.07E−03 0.41 0.49 FOOTNOTE: Each variable was tested for its association with live birth outcomes in IVF by logistic regression, which gave estimate, standard error of the estimate (S.E.), p-value, mean and standard deviation (S.D.). Results for continuous variables and categorical variables were listed in Table 1A and Table 1B, respectively. ¹Positive and negative estimates indicate association with positive and negative pregnancy outcomes, respectively. ²Number of previous clinical pregnancies as defined by positive serum human chorionic gonadotropin (hCG) or pregnancy test. ³Number of previous deliveries carried to term, 37 wks. ⁴Miscarriages refer to developmental arrest or clinical pregnancy loss at or after 5 wks gestation. Season, seemingly irrelevant, was included as a negative control.

We noted that many pairs of variables, such as age and total amount of gonadotropins used, were highly correlated with one another (Table 14). Although these findings are consistent with the presumed complex and poorly understood biological mechanisms amongst ovarian aging, ovarian hormone production and egg quality, those interactions could not be studied well by ANOVA using Chi-square statistics tests (data not shown), presumably because they do not interact in a linear fashion, or multiple conditions may affect the nature of the interactions.

We chose to analyze data and generate prediction models by constructing boosted classification trees by MART® to identify non-redundant prognostic variables. MART® is a robust method used to identify interactive structure of variables that are predictive of outcomes. The use of cross-validation and boosting in parameter selection and model assessment in MART® also preserve parsimony and prevent over-fitting. Finally, MART does not presume the absence or presence of interactions, or the nature of the interactions.

TABLE 14A and 14B Correlation Between Every Pair of Variables. Table 14A No. of No. of Total amount Total amount Total amount Age of Age of Body previous previous term Spontaneous Serum d.2 of FSH of HMg of gonadotropin patient spose Mass Index pregnancies deliveries miscarriages FSH Year (IU/ml) (IU/L) (IU/L) Pre-IVF Variables Age of patient 1.00 0.56 0.04 0.22 0.13 0.14 0.17 −0.27 0.43 0.33 0.44 Age of spose 0.56 1.00 0.01 0.10 0.09 0.06 0.08 −0.19 0.23 0.19 0.24 Body Mass Index 0.04 0.01 1.00 0.08 0.05 0.05 −0.04 0.07 0.00 0.00 0.00 No. of previous pregnancies 0.22 0.10 0.08 1.00 0.56 0.70 0.01 −0.01 0.08 0.06 0.08 No. of previous term deliveries 0.13 0.09 0.05 0.56 1.00 0.14 0.05 −0.01 0.02 0.00 0.02 Spontaneous miscarriages 0.14 0.06 0.05 0.70 0.14 1.00 −0.02 0.01 0.06 0.05 0.06 Serum d.2 FSH 0.17 0.08 −0.04 0.01 0.05 −0.02 1.00 0.03 0.35 0.28 0.36 Year −0.27 −0.19 0.07 −0.01 −0.01 0.01 0.03 1.00 −0.05 −0.06 −0.06 Pre-OR Variables Total amount of FSH (IU/ml) 0.43 0.23 0.00 0.08 0.02 0.06 0.35 −0.05 1.00 0.66 0.98 Total amount of HMg (IU/L) 0.33 0.19 0.00 0.06 0.00 0.05 0.28 −0.06 0.66 1.00 0.80 Total amount of gonadotropin (IU/L) 0.44 0.24 0.00 0.08 0.02 0.06 0.36 −0.06 0.98 0.80 1.00 Endometrial thichness (mm) −0.16 −0.12 −0.05 −0.07 0.05 −0.07 −0.11 −0.04 −0.16 −0.11 −0.16 Total no. of sperm motile after wash (mill/mL) 0.04 −0.06 −0.01 0.07 0.01 0.05 0.00 −0.11 0.01 0.01 0.02 Total no. of sperm motile before wash 0.05 −0.05 0.00 0.05 0.02 0.03 0.00 −0.08 0.03 0.03 0.03 (mill/mL) Post-IVF Variables Total no. of oocytes −0.37 −0.20 0.06 −0.04 0.00 −0.02 −0.30 0.11 −0.55 −0.44 −0.56 Percentage of normal and mature oocytes −0.20 −0.08 −0.05 −0.16 −0.09 −0.13 −0.13 −0.01 −0.06 −0.09 −0.07 Normal fertilization (%) −0.05 −0.05 −0.04 0.00 0.01 0.00 −0.06 0.04 −0.05 −0.06 −0.05 Unfertilized eggs (%) 0.01 0.03 0.03 −0.02 −0.01 −0.02 0.06 −0.08 0.04 0.03 0.04 Abnormally fertilized eggs (%) 0.06 0.03 0.01 0.04 0.00 0.02 −0.01 0.07 0.02 0.05 0.03 Total no. of embryos −0.34 −0.20 0.02 −0.03 0.00 −0.01 −0.27 0.10 −0.45 −0.36 −0.46 Blastocyst development (%) −0.35 −0.21 0.06 0.01 0.03 0.02 −0.20 0.19 −0.41 −0.32 −0.42 Compaction on d.3 (%) 0.09 0.05 −0.04 0.04 0.01 0.02 −0.02 −0.24 −0.05 −0.04 −0.05 Average no. of cells per embryo 0.00 −0.01 0.04 0.07 0.02 0.05 −0.01 −0.04 −0.06 −0.07 −0.06 No. of embryos arrested at = 4 cells −0.03 0.00 −0.01 −0.04 0.00 −0.04 0.00 0.08 0.02 0.04 0.03 No. of 8 cell embryos −0.23 −0.14 0.06 0.02 0.02 0.01 −0.22 0.02 −0.41 −0.32 −0.42 Percentage of 8 cell embryos (%) 0.03 0.01 0.03 0.05 0.01 0.02 −0.06 −0.10 −0.08 −0.06 −0.08 Cryopreserved embryos (%) −0.37 −0.24 0.03 −0.04 −0.02 −0.04 −0.19 0.11 −0.37 −0.31 −0.38 Average grade of embryos −0.05 −0.03 −0.08 0.04 0.03 0.04 −0.01 0.16 0.04 0.02 0.04 Total no. of embryos transferred 0.13 0.08 −0.03 −0.02 −0.05 −0.03 −0.13 −0.07 0.02 0.04 0.03 Average no. of cells per transferred embryo −0.16 −0.10 0.04 0.03 0.01 0.04 −0.12 −0.01 −0.21 −0.18 −0.22 Average grade of embryos transferred 0.11 0.06 −0.08 0.04 0.03 0.04 0.08 0.12 0.20 0.14 0.20 No. of transferred embryos with arrest at = 4 0.09 0.06 −0.01 −0.01 0.01 −0.03 0.08 0.04 0.15 0.13 0.15 cells No. of 8 cell embryos transferred 0.03 0.04 0.04 0.00 0.00 −0.02 −0.14 −0.10 −0.18 −0.11 −0.17 Percentage of 8 cell embryos transferred (%) −0.19 −0.10 0.04 0.00 0.01 −0.01 −0.16 −0.02 −0.30 −0.21 −0.30 Endometrial Total no. of Total no. of Percentage Normal thichness sperm motile sperm motile Total no. of of normal and fertilization (mm) after wash (mill/mL) before wash (mill/mL) oocytes mature oocytes (%) Pre-IVF Variables Age of patient −0.16 0.04 0.05 −0.37 −0.20 −0.05 Age of spose −0.12 −0.06 −0.05 −0.20 −0.08 −0.05 Body Mass Index −0.05 −0.01 0.00 0.06 −0.05 −0.04 No. of previous pregnancies −0.07 0.07 0.05 −0.04 −0.16 0.00 No. of previous term deliveries 0.05 0.01 0.02 0.00 −0.09 0.01 Spontaneous miscarriages −0.07 0.05 0.03 −0.02 −0.13 0.00 Serum d.2 FSH −0.11 0.00 0.00 −0.30 −0.13 −0.06 Year −0.04 −0.11 −0.08 0.11 −0.01 0.04 Pre-OR Variables Total amount of FSH (IU/ml) −0.16 0.01 0.03 −0.55 −0.06 −0.05 Total amount of HMg (IU/L) −0.11 0.01 0.03 −0.44 −0.09 −0.06 Total amount of gonadotropin (IU/L) −0.16 0.02 0.03 −0.56 −0.07 −0.05 Endometrial thichness (mm) 1.00 0.01 0.01 0.14 0.37 0.01 Total no. of sperm motile after wash (mill/mL) 0.01 1.00 0.62 −0.03 −0.19 0.01 Total no. of sperm motile before wash 0.01 0.62 1.00 0.01 −0.08 −0.01 (mill/mL) Post-IVF Variables Total no. of oocytes 0.14 −0.03 0.01 1.00 0.13 0.03 Percentage of normal and mature oocytes 0.37 −0.19 −0.08 0.13 1.00 −0.04 Normal fertilization (%) 0.01 0.01 −0.01 0.03 −0.04 1.00 Unfertilized eggs (%) 0.01 −0.04 −0.04 −0.01 0.05 −0.83 Abnormally fertilized eggs (%) −0.02 0.05 0.09 −0.03 −0.01 −0.35 Total no. of embryos 0.21 −0.01 −0.02 0.87 0.48 0.39 Blastocyst development (%) 0.12 0.00 −0.01 0.47 0.03 0.15 Compaction on d.3 (%) −0.01 0.01 −0.01 −0.04 0.02 0.05 Average no. of cells per embryo 0.05 0.02 0.02 0.03 0.02 −0.01 No. of embryos arrested at = 4 cells −0.04 −0.03 0.00 0.00 0.01 −0.03 No. of 8 cell embryos 0.13 0.00 −0.01 0.65 0.03 0.26 Percentage of 8 cell embryos (%) 0.06 0.01 0.04 0.06 0.01 0.05 Cryopreserved embryos (%) 0.10 0.03 0.01 0.43 0.00 0.17 Average grade of embryos 0.01 −0.04 0.01 −0.02 0.01 0.01 Total no. of embryos transferred 0.11 0.02 0.00 0.08 0.59 0.23 Average no. of cells per transferred embryo 0.10 0.01 0.00 0.28 0.02 0.11 Average grade of embryos transferred −0.05 −0.05 0.02 −0.23 −0.03 −0.06 No. of transferred embryos with arrest at = 4 −0.07 −0.02 0.02 −0.19 0.01 −0.12 cells No. of 8 cell embryos transferred 0.08 0.02 −0.01 0.29 −0.01 0.18 Percentage of 8 cell embryos transferred (%) 0.13 0.01 0.01 0.36 0.03 0.15 Table 14B Abnormally Blastocyst Average no. No. of embryos Percentage Cryopreserved Average Unfertilized fertilized Total no. of development Compaction of cells per arrested No. of 8 cell of 8 cell embryos grade of eggs (%) eggs (%) embryos (%) on d.3 (%) embryo at = 4 cells embryos embryos (%) (%) embryos Pre-IVF Variables Age of patient 0.01 0.06 −0.34 −0.35 0.09 0.00 −0.03 −0.23 0.03 −0.37 −0.05 Age of spose 0.03 0.03 −0.20 −0.21 0.05 −0.01 0.00 −0.14 0.01 −0.24 −0.03 Body Mass Index 0.03 0.01 0.02 0.06 −0.04 0.04 −0.01 0.06 0.03 0.03 −0.08 No. of previous pregnancies −0.02 0.04 −0.03 0.01 0.04 0.07 −0.04 0.02 0.05 −0.04 0.04 No. of previous term deliveries −0.01 0.00 0.00 0.03 0.01 0.02 0.00 0.02 0.01 −0.02 0.03 Spontaneous miscarriages −0.02 0.02 −0.01 0.02 0.02 0.05 −0.04 0.01 0.02 −0.04 0.04 Serum d.2 FSH 0.06 −0.01 −0.27 −0.20 −0.02 −0.01 0.00 −0.22 −0.06 −0.19 −0.01 Year −0.08 0.07 0.10 0.19 −0.24 −0.04 0.08 0.02 −0.10 0.11 0.16 Pre-OR Variables Total amount of FSH (IU/ml) 0.04 0.02 −0.45 −0.41 −0.05 −0.06 0.02 −0.41 −0.08 −0.37 0.04 Total amount of HMg (IU/L) 0.03 0.05 −0.36 −0.32 −0.04 −0.07 0.04 −0.32 −0.06 −0.31 0.02 Total amount of gonadotropin (IU/L) 0.04 0.03 −0.46 −0.42 −0.05 −0.06 0.03 −0.42 −0.08 −0.38 0.04 Endometrial thichness (mm) 0.01 −0.02 0.21 0.12 −0.01 0.05 −0.04 0.13 0.06 0.10 0.01 Total no. of sperm motile after wash (mil/mL) −0.04 0.05 −0.01 0.00 0.01 0.02 −0.03 0.00 0.01 0.03 −0.04 Total no. of sperm motile before wash −0.04 0.09 −0.02 −0.01 −0.01 0.02 0.00 −0.01 0.04 0.01 0.01 (mil/mL) Post-IVF Variables Total no. of oocytes −0.01 −0.03 0.87 0.47 −0.04 0.03 0.00 0.65 0.06 0.43 −0.02 Percentage of normal and mature oocytes 0.05 −0.01 0.48 0.03 0.02 0.02 0.01 0.03 0.01 0.00 0.01 Normal fertilization (%) −0.83 −0.35 0.39 0.15 0.05 −0.01 −0.03 0.26 0.05 0.17 0.01 Unfertilized eggs (%) 1.00 −0.24 −0.34 −0.17 −0.04 −0.02 0.05 −0.24 −0.05 −0.18 −0.01 Abnormally fertilized eggs (%) −0.24 1.00 −0.11 0.03 −0.01 0.06 −0.03 −0.04 0.00 0.00 −0.01 Total no. of embryos −0.34 −0.11 1.00 0.52 −0.02 0.02 −0.01 0.77 0.07 0.49 0.00 Blastocyst development (%) −0.17 0.03 0.52 1.00 0.00 0.25 −0.20 0.61 0.26 0.69 −0.18 Compaction on d.3 (%) −0.04 −0.01 −0.02 0.00 1.00 0.13 −0.90 0.08 0.19 0.03 −0.30 Average no. of cells per embryo −0.02 0.06 0.02 0.25 0.13 1.00 −0.82 0.33 0.57 0.22 −0.38 No. of embryos arrested at = 4 cells 0.05 −0.03 −0.01 −0.20 −0.09 −0.82 1.00 −0.27 −0.47 −0.18 0.29 No. of 8 cell embryos −0.24 −0.04 0.77 0.61 0.08 0.33 −0.27 1.00 0.53 0.60 −0.21 Percentage of 8 cell ambryos (%) −0.05 0.00 0.07 0.26 0.19 0.57 −0.47 0.53 1.00 0.23 −0.34 Cryopreserved embryos (%) −0.18 0.00 0.49 0.69 0.03 0.22 −0.18 0.60 0.23 1.00 −0.17 Average grade of embryos −0.01 −0.01 0.00 −0.18 −0.30 −0.38 0.29 −0.21 −0.34 −0.17 1.00 Total no. of embryos transferred −0.18 −0.09 0.24 −0.26 0.00 −0.09 0.06 −0.09 −0.11 −0.32 0.09 Average no. of cells per transferred embryo −0.12 0.02 0.31 0.34 0.10 0.77 −0.62 0.43 0.46 0.32 −0.26 Average grade of embryos transferred 0.06 0.00 −0.24 −0.35 −0.27 −0.37 0.27 −0.42 −0.37 −0.33 0.86 No. of transferred embryos with arrest at = 4 0.12 0.01 −0.22 −0.22 −0.06 −0.59 0.78 −0.30 −0.36 −0.20 0.16 cells No. of 8 cell embryos transferred −0.16 −0.04 0.33 0.18 0.10 0.33 −0.27 0.53 0.60 0.17 −0.18 Percentage of 8 call embryos transferred (%) −0.14 −0.01 0.40 0.44 0.13 0.42 −0.34 0.64 0.77 0.42 −0.23 Total no. of Average no. Average No. of transferred No. of 8 cell Percentage of embryos of cells per grade of embryos with arrest embryos 8 cell embryos transferred transferred embryo embryos transferred at = 4 cells transferred transferred (%) Pre-IVF Variables Age of patient 0.13 −0.16 0.11 0.09 0.03 −0.19 Age of spose 0.08 −0.10 0.06 0.06 0.04 −0.10 Body Mass Index −0.03 0.04 0.08 −0.01 0.04 0.04 No. of previous pregnancies −0.02 0.03 0.04 −0.01 0.00 0.00 No. of previous term deliveries −0.05 0.01 0.03 0.01 0.00 0.01 Spontaneous miscarriages −0.03 0.04 0.04 −0.03 −0.02 −0.01 Serum d.2 FSH −0.13 −0.12 0.08 0.08 −0.14 −0.16 Year −0.07 −0.01 0.12 0.04 −0.10 −0.02 Pre-OR Variables Total amount of FSH (IU/ml) 0.02 −0.21 0.20 0.15 −0.18 −0.30 Total amount of HMg (IU/L) 0.04 −0.18 0.14 0.13 −0.11 −0.21 Total amount of gonadotropin (IU/L) 0.03 −0.22 0.20 0.15 −0.17 −0.30 Endometrial thichness (mm) 0.11 0.10 −0.05 −0.07 0.08 0.13 Total no. of sperm motile after wash (mil/mL) 0.02 0.01 −0.05 −0.02 0.02 0.01 Total no. of sperm motile before wash 0.00 0.00 0.02 0.02 −0.01 0.01 (mil/mL) Post-IVF Variables Total no. of oocytes 0.08 0.28 −0.23 −0.19 0.29 0.36 Percentage of normal and mature oocytes 0.59 0.02 −0.03 0.01 −0.01 0.03 Normal fertilization (%) 0.23 0.11 −0.06 −0.12 0.18 0.15 Unfertilized eggs (%) −0.18 −0.12 0.06 0.12 −0.16 −0.14 Abnormally fertilized eggs (%) −0.09 0.02 0.00 0.01 −0.04 −0.01 Total no. of embryos 0.24 0.31 −0.24 −0.22 0.33 0.40 Blastocyst development (%) −0.26 0.34 −0.35 −0.22 0.18 0.44 Compaction on d.3 (%) 0.00 0.10 −0.27 −0.06 0.10 0.13 Average no. of cells per embryo −0.09 0.77 −0.37 −0.59 0.33 0.42 No. of embryos arrested at = 4 cells 0.06 −0.62 0.27 0.78 −0.27 −0.34 No. of 8 cell embryos −0.09 0.43 −0.42 −0.30 0.53 0.64 Percentage of 8 cell ambryos (%) −0.11 0.46 −0.37 −0.36 0.60 0.77 Cryopreserved embryos (%) −0.32 0.32 −0.33 −0.20 0.17 0.42 Average grade of embryos 0.09 −0.26 0.86 0.16 −0.18 −0.23 Total no. of embryos transferred 1.00 −0.14 0.16 0.06 0.39 −0.21 Average no. of cells per transferred embryo −0.14 1.00 −0.39 −0.76 0.42 0.55 Average grade of embryos transferred 0.16 −0.39 1.00 0.27 −0.30 −0.43 No. of transferred embryos with arrest at = 4 0.06 −0.76 0.27 1.00 −0.35 −0.43 cells No. of 8 cell embryos transferred 0.39 0.42 −0.30 −0.35 1.00 0.73 Percentage of 8 call embryos transferred (%) −0.21 0.55 −0.43 −0.42 0.73 1.00

IVF Treatment Time Point-Specific Prognostic Factors and Models

Consistent with our goal to facilitate real life decision-making, we used boosted tree from MART to generate three prediction models, each of which utilized variables that would be available at a specific time point during IVF planning and treatment. As shown by the schematics in FIG. 20, the Pre-IVF model was limited to 21 variables primarily pertaining to patients' baseline characteristics, clinical diagnoses; the Pre-oocyte retrieval (Pre-OR) model utilized the same 21 variables pertaining to patient's response to ovarian stimulation in addition to 9 variables used in the Pre-IVF model, for a total of 30 variables; the Post-IVF model used all variables in Pre-IVF and Pre-OR in addition to data pertaining to embryo development, and embryo parameters related to transfer or cryopreservation for a total of 57 variables.

Pre-IVF Model. MART analysis of 1879 C1 patients with respect to 21 continuous and categorical variables that are known prior to starting IVF treatment (see Table 13), showed that each of patient's age and the diagnosis of diminished ovarian reserve (DOR) alone, as well as their interaction, predicted live birth outcomes. At our center, DOR has been routinely used to describe patients who showed a history of poor response to ovarian stimulation by gonadotropins in controlled ovarian hyperstimulation/intrauterine insemination (COH/IUI) treatment. While the presence of DOR is a negative predictor for LB, it only pertained to ˜12% of the population. The rest of the patients were stratified by age. However, the model identified age thresholds (i.e. 40.5, 42.5, and 46.5) that were vastly different from thresholds (i.e. <35, 36-37, 38-40, 41-42, >42) that are arbitrarily and commonly used in the literature (ref). Overall, 5 patient subsets, hereafter populations, were discerned by this model with LB rates of 21%, 39%, 27%, 17%, and 4% for 222 (12% of all C1 patients), 690 (37%), 176 (9%), 581 (31%), and 199 (11%) patients, respectively (FIG. 21A).

Pre-OR Model. In this model, 30 variables known by the time of oocyte retrieval, from the same population comprising 1879 C1 patients, were analyzed by MART. Three independent prognostic factors were identified—total amount of gonadotropins required (TG), age, and endometrial thickness (EndoTh). Again, although each of these prognostic factors had been reported to be associated with LB outcomes, for the first time, we are objectively defining their thresholds and the nature of their potential interaction, which are critical for clinical application. Overall, this model identified 7 distinct populations with respect to their LB rates spanning 2%, 51%, 28%, 32%, 18%, 37%, and 8% for 26 (1.4% of all C1 patients), 387 (21%), 58 (3%), 200 (11%), 662 (35%), 141 (8%), and 405 (22%) patients in Populations (Pops) 1 to 7 (FIG. 21B). In addition to precisely parsed populations, the striking findings were the miniscule chance of LB outcomes for patients who had EndoTh<7.05 mm (Pop 1), those who fared poorly according to all 3 prognostic factors (Pop 5); and Age>44.5 (Pop 7). A mere combination of Pops 1, 5, and 7 showed that 1119 or ˜60% of all C1 patients had a very low LB rate of 13.5%.

Post-IVF Model. The Post-IVF model was generated by MART based on all 57 variables listed in Table 1. Of note, this analysis was restricted to 1664 of the 1879 C1 patients because 215 patients did not complete their IVF treatment and had “cycle cancellation” primarily due to suboptimal ovarian response. Four significant prognostic factors—Blast Rate, Embryo Number, TG, and EndoTh sufficed to differentiate 6 populations with LB rates ranging from 7%, 39%, 17%, 54%, 36%, and 72% for 361 (19% of patients analyzed), 96 (5.5%), 643 (40%), 316 (19%), 198 (12%), and 95 (6%) patients in Populations 1 to 6 (FIG. 21C).

Model Validation in Returning Patients and an Independent Data Set.

We validated our models by testing whether live birth rates amongst populations are significantly different in related data sets comprised of patients whose C1 did not result in a live birth and who returned for repeat treatment in 778 2^(nd)-cycles (C2) and 312 3^(rd)-cycles (C3). To further validate our results, we also tested an independent data set comprised of C1 data from 343 non-redundant patients who had IVF treatment in 2007. (See FIG. 22) Interestingly, we noted that the composition of the overall IVF patient population altered in between cycles, and between data sets.

We tested differential live birth rates amongst populations by ANOVA Chi-square test, which revealed that differential LB outcomes amongst populations remained significantly different in C2 and C3 from the 2003-2006 data set as well as C1 from the independent data set from 2007, for each of the Pre-IVF, Pre-OR, and Post-IVF models with p-values at 1.17E-50, 8.69E-71, and 1.64E-96, respectively (FIG. 23).

Then we validated our models in a different way, by testing whether the live birth rates of each prognostically-defined population was stable and unaltered amongst C1, C2, C3 of 2003-2006 data (inter-cycle, hereafter), and between C1 of 2007 and C1 of 2003-2006 data sets. The inter-cycle comparison showed that all populations remained similar for the Pre-OR and Post-IVF models; in the Pre-IVF model, only Pop 2 and Pop 4 showed that their live birth rates altered amongst cycles (p=0.02). (See Table 15 for p-values of inter-cycle comparisons.) Further, comparison of populations between the 2003-2006 and 2007 data sets indicated that the Pre-IVF and Post-IVF models, and most of the Pre-OR models have remained constant and highly reproducible (p>0.5); Pops 1 and 6 of the Pre-OR model had differential live birth outcomes between the two data sets.

TABLE 15 Live birth rates were compared between age-based control model and each of Pre-IVF, Pre-OR and Post-IVF models across populations for each age group. Age groups <35 35-37 38-40 41-42 >=43 Pre-IVF 0.6 0.1 0.01 NA NA Pre-OR 0.04 1.8E−04 3.2E−07 4.1E−05 2.1E−06 Post-IVF 3.2E−07 3.7E−05 9.5E−16 3.7E−05 1.6E−09

Collectively, our results showed that all three models were effective in stratifying patients with differential live birth rates, and this ability to stratify by prognosis is reproducible in subsequent cycles and in an independent data set, despite changes in the composition of the general IVF patient population. Further, we confirmed that the prognostic stratification and live birth prediction used in each model were reproducible and validated in an independent data set, as well as in repeat cycles of returning patients.

Models Predicted Live Birth Outcomes More Specifically than Age.

We tested whether these prediction models defined patient populations better and more specifically than an age-based control model (hereafter, control). (See Methods for age-based control model details.) We show the population-specific, observed live birth outcomes compared to live birth rates predicted by the control for each five age categories, <35, 35-37, 38-40, 41-42, and ≧43 (FIG. 24A-C). Here, age categories were defined by conventional standards used by the Society for Assisted Reproductive Technologies (SART) national registry and most of the literature (ref). These comparisons highlight the tendency for age to overestimate or underestimate live birth rates. For example, the control model tends to overestimate live birth rates in Pop 1 of the Pre-IVF model, Pops 5 and 7 of the Pre-OR model, and Pops 1 and 3 of the Post-IVF model (FIG. 24A-C). In the comparison with the Pre-OR model, control model also tends to underestimate live birth rates in Pops 2 and 3, and in age groups 41-42 and ≧43 of Pop 6, while comparison with the Post-IVF model, age tends to underestimate Pops 4 and 6.

We compared each of Pre-IVF, Pre-OR and Post-IVF models to the control with respect to the live birth rates in each of five age categories. Both the Pre-OR and Post-IVF models predicted live birth rates significantly better than the control model across populations in all five age groups (p-values range from 0.04 to 0.5E-16, see Table 15 for all p-values of these comparisons). In the Pre-IVF model, in which age is a key prognostic factor, the Pre-IVF model predicted outcomes better than the control for the age group 38-40, presumably because it also considers the diagnosis of diminished ovarian reserve (p=0.01). In summary, amongst patients who are undergoing their first fresh IVF cycle 17.7% of patients would receive more accurate and personalized live birth outcomes prediction from using the Pre-IVF model and 76% of patients would benefit from using the Pre-OR model. The utility of the Post-IVF model is to facilitate decision-making regarding subsequent IVF treatment in the event that live birth does not result from the first treatment, its use as a prediction tool for subsequent cycles is analyzed more in-depth later.

Prognostic Stratification Predicts Subsequent and Cumulative Live Birth Rates

We asked whether population assignment in C1 predicts live birth rates in C2 and the cumulative live birth rates in C2 and C3, for patients who do not have a live birth from C1. These questions precisely address the frequent scenario in which a couple needs to decide whether to repeat IVF treatment after an unsuccessful cycle. We addressed these questions by assigning patients to populations based on the Post-IVF model, followed by tracking patients' outcomes in C2 and C3. We considered both observed and hypothetical cumulative live birth rates. The observed cumulative rates were conservatively calculated based on the actual patients who returned for C2 and C3; the nominator was number of live births in C2 and C3, and the denominator was the total number of C2 cycles. The hypothetical cumulative rates were calculated based on the probability of having live birth outcomes in C2 or C3, and assumed that the patients who dropped out were no different from the ones who returned; therefore, they are not affected by the limited number of patients who chose to have C3. Specifically, C1 assignment to Pops 1 and 3 resulted in observed cumulative live birth rates of 15.1% and 18.4%, respectively, and 27.5% for Pop 5. In contrast, Pops 2, 4 and 6 had much higher cumulative live birth rates of 56.7%, 42.9%, and 75%, respectively; the hypothetical cumulative live birth rates had a trend towards being slightly higher (FIG. 25). Therefore, population assignment based on prognostic factors in C1 re-defines the IVF population into subsets that have distinct and predictable cumulative live birth rates in C2 and C3.

Gradient Boost Analysis to Identify Relative Importance of Preselected Patient Variables

We used gradient boosted machine (GBM) to perform analyses to determine the “relative influence” of each variable on live birth outcomes for all three models. Briefly, we performed 10-fold cross validation for 1879, 1879, and 1664 fresh cycles for Pre-IVF, Pre-OR, and Post-IVF models, respectively. The optimal numbers of trees were 4677, 8680, and 10,745 for Pre-IVF, Pre-OR, and Post-IVF models, respectively; 25,000 trees (i.e. more than the minimum required) were analyzed foreach model. The results are shown in Tables 16A, 16B, and 16C. The variables are ranked according to decreasing relative influence/importance such that the most important variables are ranked at the top. The numbers for relative influence add up to 100 in each model.

These GBM outputs contain thousands of trees which cannot be visualized and are conceptually too abstract for most scientific and clinical discussions. Therefore, we chose the top variables for further analysis to construct simpler tree models that could be visualized with Rpart. The advantages of simpler tree models were that they were conceptually more easily understood by scientists, clinicians, and lay people; distinct sub-populations can be characterized and subjected to further analyses to address specific questions, and to explore the utility of the models.

Tables 16A, 16B, and 16C. List of variables and their relative importance in determining live birth outcomes in the Pre-IVF, Pre-OR and Post-IVF model respectively.

TABLE 16A Pre-IVF Model Pre-IVF model Relative Variables Importance Age of patient 45.38 Diminished ovarian reserve 14.82 Age of spouse 11.55 Serum d. 3 FSH (IU/L) 10.71 Body Mass Index 6.37 Polycystic ovarian syndrome 2.88 Season 1.75 Unexplained female infertility 1.35 Spontaneous miscarriages 0.97 Year 0.89 Other causes of female infertility 0.76 No. of previous pregnancies 0.74 No. of previous term deliveries 0.64 Endometriosis 0.51 Tubal disease 0.48 Tubal ligation 0.09 Male infertility only 0.07 Uterine fibroids 0.02 Hydrosalpinx 0.01 Male infertility causes 0.01

TABLE 16B Pre-OR Model Pre-OR model Relative Variables Importance Total amount of gonadotropin 35.22 Endometrial Thickness 17.58 Age of patient 14.16 No. of sperm motile after wash 8.05 (million/mL) No. of sperm motile before wash 6.87 (million/mL) Sperm collection 6.03 Age of spouse 4.27 Body Mass Index 2.91 Serum d. 3 FSH (IU/L) 2.41 Season 0.75 Spontaneous miscarriages 0.39 Unexplained female infertility 0.39 No. of previous term deliveries 0.26 Year 0.26 No. of previous pregnancies 0.21 Other causes of female infertility 0.10 Endometriosis 0.04 Male infertility only 0.02 Tubal ligation 0.02 Polycystic ovarian syndrome 0.02 Tubal disease 0.02 Sperm from donor 0.00 Hydrosalpinx 0.00 Uterine fibroids 0.00 Male infertility causes 0.00

TABLE 16C Post-IVF Model Post-IVF model Relative Variables Importance Blastocyst development (%) 27.30 Total amount of gonadotropin 10.58 Total no. of embryos 8.95 Endometrial Thickness 7.24 Flare protocol 6.13 Average no. of cells per embryo 4.97 Catheter used 4.04 Percentage of 8 cell embryos 3.54 Serum d. 3 FSH (IU/L) 3.17 Body Mass Index 3.16 No. of sperm motile before wash 2.99 (million/mL) No. of sperm motile after wash 2.88 (million/mL) Age of patient 2.56 Average grade of embryos 2.49 Day of embryo transfer 1.88 Season 1.32 Spontaneous miscarriages 0.93 No. of previous term deliveries 0.74 Oral contraceptive pills 0.68 Sperm collection 0.58 Unfertilized eggs (%) 0.56 No. embryos arrested at = 4 cells 0.54 Compaction on day 3 0.51 Normal fertilization (%) 0.48 Abnormally fertilized eggs (%) 0.48 Percentage of normal and mature 0.48 oocytes No. of previous pregnancies 0.26 Year 0.17 Polycystic ovarian syndrome 0.12 Unexplained female infertility 0.11 Tubal disease 0.05 Male infertility only 0.05 Male infertility causes 0.03 Endometriosis 0.02 Other causes of female infertility 0.01 Uterine fibroids 0.01 Tubal ligation 0.00 Sperm from donor 0.00 Hydrosalpinx 0.00 Performance of ICSI 0.00 Assisted Hatching 0.00

Example 7 Determination of Molecular Fingerprint for Normal Vs. Abnormal Human Embryos

We successfully tested the expression of a panel of genes in dissociated blastomeres of control cryopreserved-thawed human embryos that are at the 1-cell, 4-cell, and 8-cell stages. (Patients donated those control embryos to research because they had completed their families.) We analyzed the data by considering both standard deviation and mean. The results of gene chip experiments on the 1-cell, 4-cell, and 8-cell stages are provided in FIGS. 25-30. These results show the utility of gene expression analysis at the single-cell level as well examining expression of many genes simultaneously. As such, the results show that the fingerprinting analysis for the embryos could be used to provide information that may improve prediction of live birth outcomes for subsequent IVF cycles.

The preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. The scope of the present invention, therefore, is not intended to be limited to the exemplary embodiments shown and described herein. Rather, the scope and spirit of present invention is embodied by the appended claims.

TABLE 8A Row Gene Oct4.1 Oct4.2 Oct4.3 NI1.1 NI1.2 NI1.3 NI2.1 NI2.2 NI.2.3 FoldChange MedianFDR MeanFDR T 12561 0610039J04Rik: RIKEN 726.94 952.88 925.99 702.03 806.57 331 405.8 335.4 516.81 1.682481163 0.04796748 0.09424119 11.4121 cDNA 0610039J04 gene 17702 0610040J01Rik: RIKEN 408.14 292.64 232.51 164.99 152.49 79.1 50.46 95.62 57.89 3.108117559 0.027310924 0.06003501 19.3713 cDNA 0610040J01 gene 14297 1110007M04Rik: RIKEN 1261.71 969.97 1148.54 891.24 883.27 742.9 514.8 528.3 552.68 1.643608215 0.047535211 0.09174589 11.9566 cDNA 1110007M04 gene 23774 1300003B13Rik: RIKEN 366.9 654.15 629.58 353.58 521.61 292.6 233.5 199.1 273.86 1.761395346 0.047778709 0.09288628 11.6452 cDNA 1300003B13 gene 2769 1500005A01Rik: RIKEN 190.67 162.34 88.43 60.38 43.44 74.49 60.43 32.43 37.65 2.858882197 0.048085485 0.09187593 12.0161 cDNA 1500005A01 gene 22816 1500011B03Rik: RIKEN 322.26 247.98 673.66 122.44 129.61 103.8 91.83 188.2 110.61 3.332395687 0.028446389 0.06021882 19.6218 cDNA 1500011B03 gene 22897 1500041J02Rik: RIKEN 1893.92 1849.2 1693.29 1451 1424 1116 1066 1017 1101.9 1.515255995 0.046834345 0.09180399 11.8767 cDNA 1500041J02 gene 39273 1700013H16Rik: RIKEN 758.43 675.7 737.99 758.17 463.94 313.6 215 215.7 339.42 1.884057091 0.045634921 0.08490741 12.9579 cDNA 1700013H16 gene 39378 1700080O16Rik /// 200.58 99.12 179.18 2.68 13.11 53.79 4.95 4.98 14.24 10.21610667 0.010416667 0.0375 38.9031 LOC665895 /// LOC671223 /// LOC676479: RIKEN cDNA 1700080O16 gene /// similar to melanoma antigen family A, 5 /// similar to melanoma antigen family A, 5 /// similar to melanoma antigen family A, 5 25993 1700129I15Rik: RIKEN 669.05 306.9 110.37 38.64 337.75 62.42 8.11 130.2 9.06 3.706501527 0.032414911 0.06916261 16.8302 cDNA 1700129I15 gene 1469 1810021J13Rik: RIKEN 197.73 84.01 193.51 54.69 91.43 27.17 26.09 36.55 61.85 3.191953791 0.03257329 0.06910423 16.8574 cDNA 1810021J13 gene 38853 1810044A24Rik: RIKEN 327.76 445.4 180.89 194.87 99.06 230.3 90.63 104.2 122.74 2.266582724 0.044401544 0.08662162 12.7189 cDNA 1810044A24 gene 14361 2010109N14Rik: RIKEN 2153.09 1615.8 2175.97 1431.2 1545.7 1498 990.7 1212 998.06 1.548963257 0.036834925 0.07317417 15.5482 cDNA 2010109N14 gene 12883 2010301N04Rik: RIKEN 137.6 388.98 247.94 70.02 143.76 72.7 44.83 53.42 47.03 3.587733926 0.023560209 0.0575829 21.1602 cDNA 2010301N04 gene 4342 2410022L05Rik: RIKEN 1336.22 1283.4 1702.28 919.13 704.51 611.2 198 869.9 354.78 2.363351515 0.019047619 0.04355556 28.4416 cDNA 2410022L05 gene 4343 2410022L05Rik: RIKEN 1587.18 1243 1840.86 1006.1 799.09 735.3 264.5 1067 383.1 2.195358325 0.020833333 0.04227431 29.5735 cDNA 2410022L05 gene 7831 2510042P03Rik: RIKEN 609.91 476.61 483.28 205.72 292.53 253.9 143.3 227.1 130.33 2.506046408 0.026923077 0.06301282 18.4494 cDNA 2510042P03 gene 38903 2600010E01Rik: RIKEN 303.78 312.45 368.93 57.76 100.13 37.76 33.32 102.2 59.89 5.037893122 0.01010101 0.03750842 38.2228 cDNA 2600010E01 gene 12473 2610001J05Rik: RIKEN 296.77 409.38 503.49 245.92 295.87 217.2 127.3 127.2 112.09 2.149210241 0.042988741 0.08313886 13.1993 cDNA 2610001J05 gene 17629 2610200G18Rik: RIKEN 507.41 353.97 562.56 226.7 318.05 160 138.3 150 181.72 2.424181549 0.02284264 0.05854484 20.816 cDNA 2610200G18 gene 8796 2610204L23Rik: RIKEN 2035.34 2238.2 2213.21 1158 1919.6 996.2 1310 1294 1439.4 1.598253609 0.035814607 0.07222846 15.755 cDNA 2610204L23 gene 13166 2610206B13Rik: RIKEN 225.38 66.31 200.47 99.87 45.82 54.05 28.4 45.37 49.13 3.050830647 0.03313253 0.07128514 16.2151 cDNA 2610206B13 gene 15069 2700060E02Rik: RIKEN 1283.21 1570.9 1406.02 866.04 1267.3 698.8 686.8 853.4 876.63 1.623218225 0.047315742 0.09020625 12.2015 cDNA 2700060E02 gene 12465 2810026P18Rik: RIKEN 2572.92 1625.6 2626.66 1339.2 1910.7 1650 1370 1348 1217.5 1.544918909 0.02722323 0.06469449 17.9141 cDNA 2810026P18 gene 1357 2810037C14Rik: RIKEN 1234.26 1441.4 1159.06 686.13 824.88 637.2 505.8 807.8 513.31 1.929321084 0.027184466 0.06282848 18.5328 cDNA 2810037C14 gene 7425 2810405K02Rik: RIKEN 178.7 133.85 23.59 37.21 19.15 47.42 21.42 5.11 43.31 3.872134547 0.047822374 0.09246513 11.7588 cDNA 2810405K02 gene 2836 2810429O05Rik: RIKEN 545.26 616.74 406.07 256.07 314.66 153.4 93.44 189.3 192.29 2.615411559 0.024390244 0.05095238 24.3184 cDNA 2810429O05 gene 8173 2900092E17Rik: RIKEN 364.43 535.89 536.98 201.3 208.16 223.1 249.4 258.8 279.55 2.023952855 0.034950071 0.07232525 15.8264 cDNA 2900092E17 gene 31900 3 days neonate thymus cDNA, 217.23 198.01 208.5 35.11 62.24 25.96 128.6 54.01 42.21 3.58368285 0.026156942 0.06102616 18.9222 RIKEN full-length enriched library, clone: A630060L04 product: unclassifiable, full insert sequence 23783 3110040M04Rik /// 262.9 66.64 204.12 24.31 69.95 13.99 53.82 27.08 11.49 5.319577352 0.019607843 0.04245098 28.9087 LOC668050 /// LOC668055 /// LOC671025 /// LOC671035 /// LOC671043 /// LOC671049 /// LOC676755 /// LOC676758: RIKEN cDNA 3110040M04 gene /// similar to U2- associated SR140 protein /// hypothetical protein LOC668055 /// similar to U2- associated SR140 protein /// similar to U2-associated SR140 protein /// similar to U2-associated SR140 protein /// similar to U2-associated SR140 protein /// similar to U2-associated SR140 protein /// similar to U2-associated SR140 protein 24812 3110045A19Rik: RIKEN 133.79 102.29 11.36 16.34 11.54 14.64 9.74 11.08 9.95 6.752353664 0.035664336 0.07221445 15.7371 cDNA 3110045A19 gene 41988 4930406H16Rik /// Nalp4e: 504.28 1414.9 933.88 507.4 694.22 548.5 512.1 494.6 292.39 1.871318333 0.045098039 0.08532353 12.8793 RIKEN cDNA 4930406H16 gene /// NACHT, leucine rich repeat and PYD containing 4E 25457 4930452B06Rik: RIKEN 159.43 56.45 170.72 54.77 36.42 26.26 16.28 39.2 26.39 3.879189243 0.029668412 0.06595695 17.569 cDNA 4930452B06 gene 27714 4930455F23Rik: RIKEN 534.1 677.74 522.3 346.74 399.19 274.9 281.7 256.8 176.61 1.997868651 0.047457627 0.09223446 11.7332 cDNA 4930455F23 gene 12139 4933407C03Rik: RIKEN 132.88 24.46 352.91 23.21 29.24 24.42 23.67 16.78 20.79 7.38903772 0.02374670 0.05663149 21.4433 cDNA 4933407C03 gene 5148 4933411K20Rik: RIKEN 738.65 1039.5 815.98 385.61 591.61 566 375.2 430.3 545.57 1.792608768 0.048440066 0.09399288 11.4661 cDNA 4933411K20 gene 39323 4933416M07Rik: RIKEN 131.45 240.96 376.74 164.45 78.57 97.69 70.38 90 47.91 2.729143898 0.042071197 0.08097807 13.6443 cDNA 4933416M07 gene 29217 4933427D06Rik: RIKEN 908.64 946.8 1089.77 626.62 734.75 426.3 393.3 601.6 587.3 1.747950978 0.047619048 0.09166961 11.9754 cDNA 4933427D06 gene 32880 5330427D05Rik: RIKEN 288.66 223.45 219.68 127.67 89.86 117.7 46.92 105.9 66.56 2.639125809 0.047120419 0.09182373 11.9053 cDNA 5330427D05 gene 12662 5730507H05Rik: RIKEN 812.73 648.02 809.21 424.8 297.08 456.7 492.6 353.6 405.37 1.868164517 0.035161744 0.07214721 15.7684 cDNA 5730507H05 gene 10438 5830415L20Rik: RIKEN 1798.9 1735.1 1623.57 447.1 794.05 612.1 547.7 578.6 472.45 2.988146002 0 0.02944444 58.7902 cDNA 5830415L20 gene 10605 6430548M08Rik: RIKEN 172.77 77.66 129.96 52.6 22.23 16.06 21.88 26.12 38.85 4.280297063 0.038167939 0.07466497 15.0198 cDNA 6430548M08 gene 26997 6720463M24Rik: RIKEN 217.15 218.01 225.79 73.98 49.43 68.05 56.28 107.7 70.8 3.10166827 0.032786885 0.07150025 16.1248 cDNA 6720463M24 gene 31488 7420416P09Rik: RIKEN 891.83 777.85 767.35 491.65 642.89 411.6 237.4 519.4 353.02 1.835126771 0.048171276 0.09178709 12.027 cDNA 7420416P09 gene 29615 A230048G03Rik /// 171.76 66.93 163.5 48.01 41.96 51.96 61.61 18.34 49.85 2.960217863 0.043032787 0.08315232 13.2034 LOC670614: RIKEN cDNA A230048G03 gene /// similar to CG2747-PB, isoform B 22603 A230062G08Rik: RIKEN 322.83 261.74 354.1 323.26 201.66 68.32 42.84 53.83 127.44 2.29686181 0.047858942 0.09292751 11.655 cDNA A230062G08 gene 41840 A430033K04Rik: RIKEN 1229.01 998.13 1215.48 461.08 557.03 342.2 761 837.6 205.38 2.175946907 0.016877637 0.04720113 26.7452 cDNA A430033K04 gene 15795 A830039H10Rik: RIKEN 285.01 249.94 242.98 101.83 100.81 86.69 105.9 99.37 94.16 2.642649682 0.042253521 0.0812026 13.6501 cDNA A830039H10 gene 14842 Adcy3: adenylate cyclase 3 758.96 864.83 804.58 572.29 686.9 438.5 319.3 409.5 337.76 1.757014688 0.048333333 0.09301667 11.6011 27502 Adult male medulla oblongata 149.12 176.59 33.92 30.73 59.6 50.95 19.27 31.34 26.32 3.296182576 0.042900919 0.0831018 13.1896 cDNA, RIKEN full-length enriched library, clone: 6330441D15 product: hypothetical protein, full insert sequence 42166 Agrp: Agouti related protein 231.44 178.62 94.37 33.38 179.24 13.68 1 3.54 25.21 3.940089826 0.033182504 0.07107089 16.2397 30358 AI449441: expressed 151.46 251.91 122.96 52.19 97.84 34.47 27.9 63.13 28.11 3.466802793 0.044847328 0.08782443 12.5897 sequence AI449441 27056 Akap7: A kinase (PRKA) 474.68 818.9 809.2 330.68 516.16 412.1 350.4 355.2 259.52 1.891006214 0.028520499 0.0653773 17.7396 anchor protein 7 40856 Arhgef15: Rho guanine 75.81 156.72 162.47 102.39 39.12 15.89 18.53 57.97 26.4 3.034959662 0.04506232 0.08746245 12.6344 nucleotide exchange factor (GEF) 15 14676 Arl4c /// LOC632433: ADP- 311.79 210.2 41.38 104.69 73.13 31.74 50.31 49.49 54.66 3.095269491 0.042752868 0.08291971 13.3239 ribosylation factor-like 4C /// similar to ADP-ribosylation factor-like protein 7 14653 Arpc5l: actin related protein 2473.77 2293.9 2924.51 1813.4 2433.6 1537 1353 1754 1246.7 1.517524443 0.048559671 0.0937668 11.4908 2/3 complex, subunit 5-like 40302 Arrdc3: arrestin domain 183.69 264.91 361.58 62.76 138.75 89.69 46.24 105.3 72.66 3.144010245 0.026209677 0.06090726 18.9442 containing 3 18069 Arx: aristaless related 297.32 299.7 123.78 72.45 57.19 29.97 24.05 38.12 24.48 5.853975473 0.016129032 0.03553763 46.1316 homeobox gene (Drosophila) 29021 Ascl1: achaete-scute complex 78.29 281.43 176.69 53.61 123.08 40.97 87.55 31.01 24.18 2.976748058 0.046793761 0.09179376 11.8701 homolog-like 1 (Drosophila) 7414 Atp6v1g1: ATPase, H+ 814.9 317.26 545.09 311.05 237.03 227 233.4 269.9 361.16 2.046137987 0.042708333 0.08292361 13.3161 transporting, lysosomal V1 subunit G1 27011 Atp8a1: ATPase, 113.19 302.99 336.88 111.03 98.91 55.24 45.16 134.9 41.74 3.092585368 0.024615385 0.05401026 22.9511 aminophospholipid transporter (APLT), class I, type 8A, member 1 10707 Atpbd4: ATP binding domain 4 644.58 851.86 1031.97 378.68 582.62 175.6 246.6 575.3 407.51 2.137051719 0.026785714 0.05929315 19.8453 26830 AU022751: expressed 1575.02 1805.1 1927.95 1006.1 1485.3 930.7 1148 1148 924.02 1.598423276 0.037974684 0.07783659 14.1867 sequence AU022751 28921 AU041783: expressed 728.29 1031.6 715.32 268.18 470.17 621.1 289.7 297.9 348.87 2.1562451 0.03485064 0.07223803 15.8165 sequence AU041783 17440 Aurkc: aurora kinase C 1462.84 1182.8 1533.48 1312.5 1219.2 927.9 377.4 555.4 561.63 1.687182324 0.047372954 0.09207293 11.8231 15571 Auts2: autism susceptibility 892.1 1352.7 1127.84 816.47 892.95 829.9 561.9 507.8 366.68 1.696647131 0.047493404 0.09168279 11.9562 candidate 2 8718 AW060207: expressed 432.59 609.26 574.19 250.29 379.24 218.9 259.2 166.6 184.98 2.214784968 0.026946108 0.06165669 18.8051 sequence AW060207 29405 AW146299: expressed 284.07 216.2 332.39 121.93 161.67 105.2 66.41 71.03 112.37 2.607562828 0.036290323 0.07364247 15.4019 sequence AW146299 29099 B230312I18Rik: RIKEN 420.5 374.15 459.33 169.13 94.51 275.9 97.89 101.3 61.44 3.134479828 0.016949153 0.04735876 26.7539 cDNA B230312I18 gene 11389 B930041F14Rik: RIKEN 26.1 145.4 149.78 15.65 34.72 7.96 30.02 31.98 43.39 3.924749572 0.036096257 0.07358289 15.378 cDNA B930041F14 gene 35357 B930096F20Rik: RIKEN 232.53 102.36 229.72 30.99 16.44 13.59 17.81 40.92 54.55 6.478600115 0.010309278 0.03721649 38.8416 cDNA B930096F20 gene 33323 B930096F20Rik: RIKEN 162.51 79.13 176.86 11.2 5.38 6.12 14.66 19.82 13.65 11.81702668 0.018691589 0.03785047 36.9537 cDNA B930096F20 gene 30001 BB176347: Expressed 141.82 106.11 79.54 18.32 14.54 23.04 8.15 16.92 11.44 7.087328211 0.029616725 0.06619048 17.5516 sequence BB176347 27229 BC010981: cDNA sequence 388.39 149.2 438 121.27 178.69 160.1 120.7 85.02 190.36 2.279043147 0.03271028 0.07022845 16.5397 BC010981 10371 BC021367: cDNA sequence 255.84 599.36 133.32 56.72 58.42 9.17 12.43 144.6 45.71 6.045808997 0.015151515 0.03744949 34.4898 BC021367 10893 BC022623: cDNA sequence 784.51 724.29 716.83 301.14 357.98 339.1 388.4 240.7 107.29 2.566144551 0.021912351 0.04861886 26.0618 BC022623 28308 BC047219: cDNA sequence 402.73 298.41 481.25 99.48 304.76 138.3 227.8 47.95 55.07 2.707649679 0.02690583 0.05922272 19.8718 BC047219 31719 BC052883: cDNA sequence 3547.69 3957.6 3518.81 3150.9 2830 3065 843.8 1089 690.96 1.889427057 0.024390244 0.05562782 21.7701 BC052883 14991 Bcas2: breast carcinoma 933.79 898.82 1023.13 656.47 683.52 725.1 238.6 384.1 299.55 1.911914063 0.037546934 0.07496454 14.8965 amplified sequence 2 4790 Blcap: bladder cancer 1031.43 970.72 1005.09 398.98 455.59 428.7 593.8 433.6 467.82 2.1646422 0.025236593 0.0543428 23.1594 associated protein homolog (human) 7998 Btf3: basic transcription factor 3 1578.04 1824.5 1702.45 1348.1 1356.3 1018 743.3 874.9 818.67 1.657623607 0.036809816 0.07552147 14.7389 27083 C030048B08Rik: RIKEN 408.49 460.05 549.24 205.03 223.41 242.7 206.1 243.9 160.9 2.211756263 0.036991369 0.07569667 14.7567 cDNA C030048B08 gene 31101 C330046E03: hypothetical 4819.33 3225.1 3559.24 755.8 537.22 920.6 495.6 490.6 1006.3 5.517476831 0 0.005 199.636 protein C330046E03 43660 C80008: expressed sequence 387.88 488.55 927.38 95.78 305.61 74.02 92.37 277.2 122.15 3.730232751 0.018867925 0.03821803 32.1199 C80008 41465 C87977: expressed sequence 1813.37 1754 1731.6 1381 1479.5 1226 879 1054 758.51 1.563607178 0.0472103 0.09198283 11.8126 C87977 22912 Calcocol: calcium binding 551.7 236.85 422.22 259.49 280.12 113.5 190.8 154.3 163.4 2.084497585 0.044790652 0.08589094 12.8067 and coiled coil domain 1 8101 Camk2g: calcium/calmodulin- 336.31 254.03 256.42 116.66 94.65 136.1 97.12 109.2 105.92 2.567339761 0.04613936 0.08864721 12.4665 dependent protein kinase II gamma 11172 Car9: carbonic anhydrase 9 471.81 315.93 321.74 92.43 324.34 121.6 91.77 148.2 106.79 2.507101133 0.045 0.08457333 13.0189 270 Carhsp1: calcium regulated 783.29 492.05 805.9 323.58 378.15 367.8 428.5 461.3 410.2 1.756676458 0.038106236 0.077602 14.2229 heat stable protein 1 15424 Ccdc102a /// LOC672218: 88.88 90.52 37.42 3.07 8.66 4.42 4.14 2.85 2.42 16.96557121 0.027027027 0.06286358 18.4783 coiled-coil domain containing 102A /// similar to CG31638- PA 4096 Ccdc56: coiled-coil domain 392.74 395.1 319.83 208.46 301.88 148.4 177.1 110 108.37 2.101282392 0.044310171 0.08402148 13.0746 containing 56 22624 Ccdc69: Coiled-coil domain 962.65 1366.1 1349.11 634.59 688.1 744 606.2 369.6 463.47 2.098090669 0.019230769 0.0436859 28.4695 containing 69 22741 Ccdc69: coiled-coil domain 1132.93 1623.1 1851.99 805.4 1046.3 856 984.6 482 775.42 1.861933951 0.022535211 0.05503286 22.1289 containing 69 22623 Ccdc69: coiled-coil domain 1050.67 1566.1 1589.84 762.24 1001.9 968.9 918.1 524.8 763.31 1.703329676 0.027079304 0.06286912 18.4874 containing 69 16411 Ccni: cyclin I 493.47 644.26 702.9 315.9 404.45 474.9 206.1 318.3 253.34 1.865932038 0.042944785 0.08317314 13.192 16410 Ccni: cyclin I 995.58 940.06 798.15 555.77 798.27 475.2 498.2 513.8 309.27 1.735447687 0.045499505 0.08530828 12.922 44690 Ccnjl: cyclin J-like 710.33 626.07 346.33 315.27 210.57 294 79.62 182.2 113.19 2.816638072 0.017647059 0.03870588 31.472 329 Cd24a: CD24a antigen 1205 1433.8 1104.89 719.21 978.74 647.6 776.5 731.8 580.28 1.688576461 0.047178538 0.08963306 12.3197 6122 Cdc25b: cell division cycle 25 1318 1113.9 1472.91 1078.3 923.92 886.1 576.7 563.7 362.23 1.778541969 0.036144578 0.07362784 15.3818 homolog B (S. cerevisiae) 15802 Cdc9111: CDC91 cell division 49.58 345.26 607.45 52.03 65.68 20.93 52.8 45.12 27.03 7.604916727 0 0.03 60.8874 cycle 91-like 1 (S. cerevisiae) 12970 Cdca1: cell division cycle 674.36 667 543.88 296.75 413.81 246.4 141.6 321.8 221.52 2.296412693 0.022038567 0.05520661 21.9807 associated 1 42049 Cdk9: cyclin-dependent 139.64 199.95 196.21 14.31 19.14 29.4 35.55 8.3 51.82 6.76003028 0.014285714 0.03807143 33.6461 kinase 9 (CDC2-related kinase) 8112 Cdkal1: CDK5 regulatory 879.67 767.38 813.54 253.82 513.83 385.5 494.5 208.3 137.41 2.468897841 0.022177419 0.04872312 26.1509 subunit associated protein 1- like 1 3196 Cebpb: CCAAT/enhancer 132 304.11 204.27 35.5 57.66 60.4 8.94 15.35 29.75 6.169364162 0.018404908 0.03862986 31.7317 binding protein (C/EBP), beta 19532 Chchd5: coiled-coil-helix- 220.46 43.46 183.56 95.26 39.57 75.13 40.76 8.84 10.24 3.317123795 0.042857143 0.0835 13.1659 coiled-coil-helix domain containing 5 21181 Chchd7: coiled-coil-helix- 143.11 45.85 147.48 54.41 37.61 40.61 18.63 32.67 27.57 3.181465721 0.045320197 0.08514614 12.9126 coiled-coil-helix domain containing 7 14624 Chd4: chromodomain helicase 618.5 949.18 1142.49 391 589.16 319.2 415.8 423.6 527.37 2.033097654 0.0243309 0.05852393 20.5004 DNA binding protein 4 15480 Chd4: chromodomain helicase 1585.68 1818.1 1935.42 1226.8 1598.3 1198 946.6 909.1 980.36 1.556702038 0.044834308 0.0858642 12.8114 DNA binding protein 4 15075 Clu: clusterin 196.31 133.06 97.6 58.66 66.23 26.33 41.53 27.45 12.04 3.676972098 0.04567079 0.08815414 12.5518 2308 Cml1: camello-like 1 47.86 117.93 133.93 4.92 25.59 4.56 62.29 5.09 4.57 5.601196038 0.032520325 0.06910569 16.8467 14516 Cnot3: CCR4-NOT 796.98 668.81 778.76 366.48 721.23 392.7 402.2 266.4 437.76 1.735481277 0.048182587 0.09296422 11.6855 transcription complex, subunit 3 3016 Cops7b: COP9 (constitutive 630.4 592.56 784.56 381.57 313.14 269.3 386 255.5 166.93 2.265261447 0.027422303 0.06459476 17.9807 photomorphogenic) homolog, subunit 7b (Arabidopsis thaliana) 9970 Csrp1: cysteine and glycine- 592.11 830.02 1000.51 402.09 254.56 515.3 117.8 186.2 282.36 2.755708736 0.014388489 0.03784173 33.681 rich protein 1 42439 Cxcl1: chemokine (C—X—C 22.86 80.3 90.94 1.97 4.77 2.02 4.71 2.48 4.31 19.16090819 0.033639144 0.07090724 16.3534 motif) ligand 1 3504 Cxcl1: chemokine (C—X—C 47.52 119.73 89.85 17.25 11.6 15.44 9.7 10.43 6.75 7.224954335 0.036904762 0.07630159 14.5178 motif) ligand 1 16786 Cxcr4: chemokine (C—X—C 358.53 513.32 197.69 121.26 183.91 87.45 18.1 32.91 17.61 4.637672361 0.010526316 0.03778947 38.9113 motif) receptor 4 30909 Cyp11a1: cytochrome P450, 258.01 292.08 442.1 107.55 178.36 106.1 178.5 12.51 54.95 3.11031348 0.032051282 0.06915064 16.7746 family 11, subfamily a, polypeptide 1 41238 Cypt3: cysteine-rich 423.83 155.74 395.11 142.52 146.78 84.29 153.7 281.9 54.27 2.257667006 0.036855037 0.07558149 14.7418 perinuclear theca 3 17076 D10Jhu81e: DNA segment, 1166.3 278.18 584.98 41.06 273.73 194.1 342.2 66.45 240.74 3.504143933 0.01744186 0.0394186 31.3457 Chr 10, Johns Hopkins University 81 expressed 21185 D10Wsu102e: DNA segment, 2792.95 2498.7 2814.16 1716.1 1847 1338 1962 1712 1576.6 1.596805904 0.026666667 0.06302222 18.3654 Chr 10, Wayne State University 102, expressed 31660 D11Ertd497e: DNA segment, 1363.15 1027.4 1189.28 742.66 758.15 478.8 680.6 595 536.27 1.888339413 0.027726433 0.06448552 18.0557 Chr 11, ERATO Doi 497, expressed 32944 D130073L02Rik: RIKEN 1475.86 1476.2 1683.68 818.11 1061.5 984.4 665.5 689 969.73 1.787029488 0.03422619 0.0715377 16.1158 cDNA D130073L02 gene 19130 D14Ertd500e: DNA segment, 681.58 601.92 716.43 390.44 459.16 256.8 360.4 265.9 425.26 1.853614907 0.045226131 0.08424791 13.0523 Chr 14, ERATO Doi 500, expressed 29688 D2Ertd612e: DNA segment, 319.43 176.06 370.14 220.95 120.36 106 116.2 108.1 103.63 2.233105886 0.043294615 0.08247448 13.4481 Chr2, ERATO Doi 612, expressed 7623 D2Ertd750e: DNA segment, 394.9 506.08 652.28 243.42 291.26 438 219.8 255.7 110.89 1.9925724 0.047619048 0.09278752 11.6257 Chr 2, ERATO Doi 750, expressed 17383 Dbndd1: dysbindin 464.15 301.44 304.82 104.24 166.01 137.6 190.5 70.39 112.63 2.739969027 0.037174721 0.07516316 14.8291 (dystrobrevin binding protein 1) domain containing 1 41824 Dbx1: developing brain 276.19 187.2 124.35 38.52 58.77 7.62 29.55 11.63 10.84 7.49047346 0.01459854 0.03824818 33.796 homeobox 1 6290 Dcp1a: decapping enzyme 577.73 499.84 520.9 251.84 361.9 184 289.1 278.2 245.94 1.984530675 0.04600939 0.08865102 12.4452 542 Dctn3: dynactin 3 540.25 352.08 532.14 252.9 202.65 271.3 222 154 123.8 2.322461258 0.02244389 0.05806318 20.7509 1811 Ddit3: DNA-damage 499.34 650.01 844 254.47 351.31 188.1 199 274.8 371.53 2.432175213 0.022727273 0.05471591 22.2271 inducible transcript 3 9363 Ddx19a /// Ddx19b: DEAD 1578.61 1941.1 1533.78 1167.2 1152.7 885.9 897.4 1007 1064.7 1.636896915 0.048 0.09173926 12.0151 (Asp-Glu-Ala-Asp) box polypeptide 19a /// DEAD (Asp-Glu-Ala-Asp) box polypeptide 19b 2222 Ddx19a: DEAD (Asp-Glu-Ala- 1009.15 1114.6 1292.36 497.39 638.59 587.9 581.9 501.6 556.5 2.031071632 0.024154589 0.0584219 20.4566 Asp) box polypeptide 19a 36061 Dgat1: diacylglycerol O- 289.38 324.34 39.41 98.71 107.58 55.58 34.36 61.27 22.93 3.43364088 0.027600849 0.059908 19.4349 acyltransferase 1 24651 Dhfr: dihydrofolate reductase 426.78 75.47 340.75 63.57 73.72 47.34 58.38 22.96 36.07 5.582042114 0.018867925 0.03471698 49.1336 16466 Dhrs3: 175.77 358.46 397.37 163.62 207.39 44.67 59.21 66.67 115.31 2.836482105 0.02247191 0.05490637 22.1263 dehydrogenase/reductase (SDR family) member 3 36303 Diras2: DIRAS family, GTP- 83.58 244.42 311.89 57.09 96.41 29.57 84.61 77.33 98.72 2.884141257 0.03164557 0.06949895 16.6642 binding RAS-like 2 14159 Dmpk: dystrophia myotonica- 130.39 64.65 251.65 43.94 24.65 45.01 36.88 47.29 31.12 3.903097558 0.044573643 0.08648256 12.7504 protein kinase 18463 Dnajb5: DnaJ (Hsp40) 173.41 174.8 38.49 23.48 43.07 40.6 23.62 34.57 27 4.021004471 0.024943311 0.05890401 20.0001 homolog, subfamily B, member 5 1165 Dnalc4: dynein, axonemal, 627.08 485.5 527.62 152.51 208.44 124.3 259.5 384 378.63 2.176154117 0.037783375 0.07515533 14.9173 light chain 4 4618 Dscr6: Down syndrome 364.43 202.42 53.05 100.55 71.25 41.67 57.79 52.26 26.72 3.539858383 0.033383915 0.07102175 16.2903 critical region homolog 6 (human) 14348 Dsp: desmoplakin 348.74 368.07 172.59 17.12 59.21 37.98 120.1 62.81 35.6 5.344951923 0.018181818 0.03509091 48.1504 44606 Dynlt3: dynein light chain 1184.16 850.7 1225.34 804.47 862.49 821.8 513.8 484.1 546.26 1.616793787 0.044487427 0.0865087 12.7286 Tctex-type 3 30501 E130311K13Rik: RIKEN 292.14 72.05 149.12 73.07 44.21 47.25 43.95 46.76 53.87 3.321212513 0.048373645 0.09281346 11.6139 cDNA E130311K13 gene 1360 Egr1: early growth response 1 863.82 594.38 874.96 651.4 743.85 349.3 362.2 301.7 296.64 1.725097598 0.047790803 0.0904749 12.1522 28198 Ehd2 /// LOC673251: EH- 552.22 499.34 187.9 118.31 170.8 197.3 120 329.7 107.65 2.375217983 0.024691358 0.0582963 20.6613 domain containing 2 /// similar to EH-domain containing 2 3769 Ehf: ets homologous factor 422.95 299.88 362.77 181.23 308.34 201 118.5 82.28 115.52 2.156471301 0.048128342 0.09172906 12.0251 6059 Eif2ak1: eukaryotic 601.03 422.26 534.76 313.33 270.08 133.6 249.2 221.6 232.52 2.194034895 0.032019704 0.06823755 16.968 translation initiation factor 2 alpha kinase 1 22574 Eif2b1: eukaryotic translation 639.36 591.13 452.83 426.81 356.95 299.3 292.9 218.6 271.63 1.804037146 0.047939445 0.09294365 11.6628 initiation factor 2B, subunit 1 (alpha) 41276 Emx2: empty spiracles 234.91 298.01 341.22 97.13 165.98 119.9 85.52 182 66.68 2.437578428 0.037585421 0.078265 14.0886 homolog 2 (Drosophila) 27167 Faah: fatty acid amide 147.03 240.15 277.1 108.99 47.52 58.21 61.45 124.1 50.02 2.950192081 0.030252101 0.06778151 17.1504 hydrolase 316 Fabp5 /// LOC628298 /// 1266.08 1469.8 1868.49 809.42 1034.2 1028 272.5 598 286.82 2.285431361 0.019417476 0.04377023 28.5422 LOC637129 /// LOC669559 /// LOC672321: fatty acid binding protein 5, epidermal /// similar to Fatty acid- binding protein, epidermal (E- FABP) (Psoriasis-associated fatty acid-binding protein homolog) (PA-FABP) (Keratinocyte lipid-binding protein) /// similar to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding protein homolog) (PA-FABP) (Keratinocyte lipid-binding protein) /// similar to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding protein homolog) (PA-FABP) (Keratinocyte lipid-binding protein) /// similar to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding protein homolog) (PA-FABP) (Keratinocyte lipid-binding protein) 317 Fabp5: fatty acid binding 436.27 439.2 537.34 241.63 390.24 301.4 62.47 184.3 99.47 2.208430053 0.048387097 0.09106631 12.0981 protein 5, epidermal 1371 Fabp9: fatty acid binding 409.89 270.29 333.46 189.49 58.21 125.5 90.91 122.6 177.68 2.652431605 0.029900332 0.06765227 17.1013 protein 9, testis 38293 Fank1: fibronectin type 3 and 2043.72 1333.2 2424.93 1297.9 895.96 1029 224.5 906.6 897.4 2.20974613 0.014705882 0.03808824 33.9309 ankyrin repeat domains 1 38294 Fank1: fibronectin type 3 and 924.97 617.49 1115.41 530.43 486.47 334.5 325.3 374.2 450.52 2.125114436 0.022792023 0.0548433 22.228 ankyrin repeat domains 1 28859 Fbxw14 /// LOC668758 /// 1689.47 1449.1 1379.4 771.7 977.11 774 924.7 979.8 930.52 1.686457855 0.04250797 0.08190932 13.5148 LOC673189: F-box and WD- 40 domain protein 14 /// similar to F-box and WD-40 domain protein 14 /// similar to F-box and WD-40 domain protein 14 17631 Fetub: fetuin beta 339.98 98.9 176.78 28.16 22.02 28.89 47.19 149.6 27.08 4.064701416 0.030050083 0.06791319 17.1106 18896 Fgf1: fibroblast growth factor 1 681.86 369.41 720.7 327.77 349.5 445.6 311.8 285.3 249.7 1.799219174 0.038548753 0.07857143 14.042 16430 G6pdx: glucose-6-phosphate 1968.98 1787.5 2156.26 787.91 1751.9 1060 912.4 963.3 1065.4 1.807953743 0.022900763 0.05866836 20.8236 dehydrogenase X-linked 20610 Galm: galactose mutarotase 325.39 308.96 339.4 107.5 239.54 178.8 127.7 148.9 72.69 2.225459947 0.047488584 0.09021005 12.2255 32346 Gas2l1: growth arrest-specific 161.84 235.35 19.91 17.07 61.3 43.92 20.12 11.33 52.21 4.050497694 0.045454545 0.0852668 12.9177 2 1ike 1 12777 Gch1: GTP cyclohydrolase 1 398.77 412.01 533.59 236.21 254.72 224.9 133.7 148.3 134.69 2.37426818 0.0373599 0.07496056 14.8721 38302 Ghitm: Growth hormone 167.4 64.72 61.47 5.07 13.4 2.06 3.34 4.13 8.35 16.15350757 0.037714286 0.07841524 14.1066 inducible transmembrane protein 27801 Gm129: gene model 129, 962.68 506.38 860.85 158.2 317.4 272.4 320.2 434.4 279.11 2.615437289 0.014925373 0.03823383 34.0765 (NCBI) 31138 Gm1568: gene model 1568, 543.23 1089.3 807.32 324.93 568.66 388.6 233.9 198.5 219.96 2.522390451 0.01754386 0.04565789 27.2403 (NCBI) 16058 Gm428 /// LOC623180 /// 1914.89 1546.2 1987.58 718.98 1301.8 938 1086 1344 986.94 1.709161859 0.026694045 0.06009582 19.1631 LOC623197 /// LOC623210 /// LOC623219: gene model 428, (NCBI) /// hypothetical LOC623180 /// hypothetical LOC623197 /// hypothetical LOC623210 /// hypothetical LOC623219 17875 Gna14: guanine nucleotide 300.19 342.97 390.91 109.58 273.46 141.3 122.7 96.2 128.54 2.372264281 0.037558685 0.07721831 14.351 binding protein, alpha 14 27857 Gnaz: guanine nucleotide 291.26 148.83 411.78 101.45 157.63 114.7 126.2 93.34 143.95 2.311190092 0.045837231 0.08869036 12.4247 binding protein, alpha z subunit 3764 Gnb4: guanine nucleotide 800.06 500.22 743.39 483.85 537.75 253.1 157.9 393.7 258.05 1.960947433 0.033674963 0.07097609 16.075 binding protein, beta 4 1723 Gng3: guanine nucleotide 1141.11 1006.1 938.92 376.96 611.22 390.9 606.5 482.2 588.54 2.019579614 0.026369168 0.06075727 19.0026 binding protein (G protein), gamma 3 subunit 38463 Gng4: guanine nucleotide 29.31 68.46 318.22 20.93 10.51 15.87 14.53 12.26 10.91 9.786848606 0.04808476 0.09437924 11.4171 binding protein (G protein), gamma 4 subunit 14851 Gng5: guanine nucleotide 751.62 1021.2 1032.02 380.3 617.1 541.3 307.9 450.5 359.29 2.111806714 0.021428571 0.05125 24.5286 binding protein (G protein), gamma 5 subunit 19438 Gprc5b: G protein-coupled 306.88 118.93 6.69 4.77 9.28 5.32 8.02 2.74 32.26 13.86440135 0.023346304 0.05102464 25.4672 receptor, family C, group 5, member B 14609 Grina: glutamate receptor, 1034.42 812.15 1228.38 477.25 540.8 546.5 285.4 670.3 531.6 2.015164771 0.027088036 0.0592927 19.9298 ionotropic, N-methyl D- asparate-associated protein 1 (glutamate binding) 15539 Grn: granulin 1352.59 514.79 1057.39 324.87 349.47 237.6 326.6 429.6 434.48 2.782090489 0.012820513 0.03683761 41.8478 21945 Grn: granulin 1042.32 422.35 831.7 282.08 293.46 176.8 252.5 333.1 327.99 2.756746699 0.017094017 0.03763533 35.8799 44280 Gyg: glycogenin 1636.36 1537.6 1912.79 587.38 955.09 642.4 640.7 735.8 665.37 2.406956662 0.01754386 0.03795322 36.2379 16505 Gyg: glycogenin 1843.18 1330 1474.57 451.38 788.27 545 633.2 808.2 736.02 2.346160253 0.01863354 0.03867495 31.8723 21695 Hadhsc: L-3-hydroxyacyl- 176.86 172.31 47.15 7.97 25.17 8.67 37.31 48.56 24.68 5.202415332 0.024475524 0.05073427 24.4128 Coenzyme A dehydrogenase, short chain 20748 Hba-a1: hemoglobin alpha, 145.01 91.26 185.79 31.03 31.41 48.27 14.05 70.23 28.93 3.769739193 0.037667072 0.07575132 14.6733 adult chain 1 34409 Hdlbp: High density 65.43 20.02 222.9 4.86 15.41 2.9 23.01 5.26 6.4 10.66217151 0.048414023 0.09280467 11.6202 lipoprotein (HDL) binding protein 21722 Hes5: hairy and enhancer of 77.81 670.65 255.74 37.89 6.51 4.11 5.4 49.42 10.01 17.72013411 0 0.03571429 76.3251 split 5 (Drosophila) 14548 Hes6: hairy and enhancer of 874.59 449.21 52.72 14.43 115.08 53.85 47.95 155.1 45.4 6.375581853 0 0.03063063 57.3556 split 6 (Drosophila) 294 Hey1: hairy/enhancer-of-split 782.14 951.79 1330.97 370.68 579.38 458.1 340.9 320.2 328.5 2.556469371 0.019900498 0.04260365 29.0333 related with YRPW motif 1 40573 Hist2h2be: histone 2, H2be 45.26 112.92 234.65 9.51 47.79 32.3 12.23 14.75 13.01 6.062659156 0.032357473 0.07042116 16.4512 15290 Hk1: hexokinase 1 97.53 40.72 292.16 23.48 13.09 10.02 17.7 8.41 70.37 6.016775005 0.045279383 0.08702954 12.6818 1997 Hnmt: histamine N- 291.41 218.29 287.13 133.75 161.6 140.3 63.03 104.4 82.11 2.325899764 0.042619543 0.08295565 13.3018 methyltransferase 20448 Hoxa3: homeo box A3 67.37 168.06 195.07 30.43 54.67 3.04 114.4 21.42 18.67 3.549198236 0.036643026 0.07695823 14.4359 38029 Hspa12a: heat shock protein 99.91 395.12 430.36 63.95 34.34 2.89 11.27 190.3 15.72 5.810743776 0 0.02886179 56.2068 12A 20415 Hspa1a: heat shock protein 665.51 521.22 682.91 384.53 418.07 300.9 177.6 256.6 240.21 2.103200405 0.026717557 0.06280534 18.4144 1A 20345 Hspa1b: heat shock protein 1356.32 1044 604.27 612.34 519.36 458.8 326.2 890.6 200.5 1.997912074 0.030201342 0.06785794 17.1351 1B 11286 Hspa1b: heat shock protein 603.12 550.63 273.69 292.64 253.66 243.1 178.7 397.6 109.8 1.934869094 0.04518664 0.08519974 12.8968 1B 1396 Hspa2: heat shock protein 2 1671.68 1450.9 1466.81 768.33 1325.6 888 653 1010 758.87 1.698705433 0.041845494 0.08110515 13.6108 3507 Icos1: icos ligand 698.31 470.26 803.79 259.27 478.54 329.9 299.9 350.5 227.76 2.027216478 0.030508475 0.06688701 17.2922 14244 Id2: inhibitor of DNA binding 2 159.2 175.61 225 87.31 76.02 44.55 20.82 47.44 37.67 3.567827666 0.036262204 0.0725709 15.7007 3942 Ier3: immediate early 135.39 282.8 200.44 43.458 88.87 51.5 102.8 52.75 30 3.349649403 0.032407407 0.07047325 16.4563 response 3 5812 Igh-VJ558 /// LOC238447 /// 796.82 447.15 483.63 357.22 539.3 266.5 77.64 114.2 116.29 2.348686715 0.047531993 0.09001828 12.2414 LOC544903 /// LOC544907: immunoglobulin heavy chain (J558 family) /// similar to immunoglobulin heavy chain variable region /// similar to immunoglobulin mu-chain /// similar to anti-poly(dC) monoclonal antibody heavy chain 18787 Ing3: inhibitor of growth 797.55 862.17 1017.87 636.48 680.07 589 200.3 400.2 302.52 1.906748702 0.041980624 0.08096161 13.6303 family, member 3 40325 Insig1: insulin induced gene 1 2692.54 2321.2 2684.68 1690.3 1802.6 1778 1643 1631 1533.5 1.527618507 0.035150646 0.07234338 15.8472 16512 Irf1: interferon regulatory 789.3 575.41 867.38 269.32 522.82 348.8 278.6 292.6 194.46 2.341447296 0.022900763 0.05101781 25.2531 factor 1 2812 Irx3: Iroquois related 348.55 332.29 138.19 5.68 121.77 63.47 127.6 69.42 60.1 3.656465546 0.017857143 0.04482143 27.5757 homeobox 3 (Drosophila) 18056 Itga9: integrin alpha 9 602.24 988.31 1038.91 552.93 662.74 418.5 555.2 457.9 546.34 1.646726537 0.042268041 0.08298625 13.2595 1704 Jun: Jun oncogene 824.08 580.75 436.92 74.84 119.42 26.57 109.4 37.89 28.35 9.290272138 0 0.02583333 113.684 38760 Kalrn: kalirin, RhoGEF 455.34 326.78 526.39 276.27 277.62 210.1 85.33 54.31 126.1 2.541487006 0.028697572 0.05972774 19.7266 kinase 17540 Kcnq1: potassium voltage- 253.97 94.35 476.89 62.84 42.18 56.37 133.6 55.74 24.75 4.395844986 0.020661157 0.04779614 26.4773 gated channel, subfamily Q, member 1 38646 Kif13a: Kinesin family 341.25 421.32 771.62 218.81 258.08 529 77.71 47.73 84.33 2.524106842 0.047169811 0.09193539 11.8117 member 13A 25517 Kif24: kinesin family member 338.53 277.95 398.92 132.82 85.27 159.4 147.6 148.5 106.19 2.604290899 0.029801325 0.06786424 17.0703 24 16345 Klhl13: kelch-like 13 1515.8 1527.5 1239.11 1454.6 785.49 962.1 538.2 329.8 445.64 1.896626556 0.026966292 0.05925094 19.8985 (Drosophila) 13958 Ldhb: lactate dehydrogenase B 2740.69 2312.3 3295.47 1762 2507 1685 1417 2027 1678.1 1.507554068 0.045105566 0.087508 12.6371 5980 Ldlr: low density lipoprotein 335.33 308.94 424.04 117.76 245.41 172 99.41 87.75 147.65 2.456054441 0.038283063 0.07753674 14.2499 receptor 29964 Ldlrad3: low density 349.24 268.52 370.69 153.24 103.08 147.7 93.05 223.7 96.65 2.418344628 0.033873343 0.07123711 16.0846 lipoprotein receptor class A domain containing 3 916 Llgl1: lethal giant larvae 1297.45 1170.9 1328.72 919.12 927.65 845 526.8 632.3 506.16 1.742963703 0.036451169 0.07264099 15.6391 homolog 1 (Drosophila) 21355 Lmo7: LIM domain only 7 2299.11 2394 2530.26 1703.4 2212.2 1824 1271 1373 1270.7 1.496467727 0.04749788 0.09230421 11.7338 32615 LOC240444: Similar to 218.5 275.91 425.72 86.21 127.38 61.45 46.82 105.4 143.32 3.22507492 0.026315789 0.06088394 18.9799 Potassium voltage-gated channel subfamily G member 2 (Voltage-gated potassium channel subunit Kv6.2) (Cardiac potassium channel subunit) 14891 LOC545161 /// LOC637273: 1517.86 1912.8 1961.88 1213.5 1373.7 1085 657.6 832.6 661.9 1.851793474 0.023890785 0.05119454 24.0588 similar to Peroxiredoxin 1 (Thioredoxin peroxidase 2) (Thioredoxin-dependent peroxide reductase 2) (Osteoblast specific factor 3) (OSF-3) (Macrophage 23 kDa stress protein) /// similar to Peroxiredoxin-1 (Thioredoxin peroxidase 2) (Thioredoxin- dependent peroxide reductase 2) (Osteoblast-specific factor 3) (OSF-3) (Macrophage 23 kDa stress protein) 19912 LOC574530: metallothionein 226.98 259.54 118.5 143.89 63.21 9.37 10.47 15.52 12.43 4.747302758 0.018957346 0.04349131 28.4084 1K 34813 LOC627488 /// LOC627520 3712.88 3330.1 4059.81 2547.1 3079.4 2572 1852 2591 2371.8 1.479044054 0.036719706 0.07589147 14.7015 /// LOC667692 /// LOC667695 /// LOC673990: similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) 36676 LOC665521 /// LOC665546 1690.74 1078.8 1867.35 435.93 1040.6 413.3 298 288.9 409.86 3.212720848 0 0.02811594 69.6907 /// LOC665755 /// LOC666203: similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 35372 LOC666806: similar to X- 1437.33 1258.1 1431.69 830.47 904.29 911.7 639.8 803.3 394.95 1.840602429 0.028508772 0.06025585 19.6427 linked eukaryotic translation initiation factor 1A 23907 LOC677447: similar to 169.23 96.13 289.52 47.67 49.17 46.11 50.1 30.45 38.54 4.235078614 0.026415094 0.06295597 18.313 RIKEN cDNA 5730590G19- like 2237 Lypd3: Ly6/Plaur domain 398.36 354 401.18 228.49 210.36 118.7 246.3 99.17 235.65 2.026189368 0.047863248 0.09232479 11.7737 containing 3 22323 Lysmd3: LysM, putative 453.85 368.82 661.12 92.84 321.95 197.1 125 290.1 91.81 2.6523721 0.026748971 0.0601166 19.1722 peptidoglycan-binding, domain containing 3 14392 Marcks11 /// LOC673071: 1185.33 1143.2 1024.39 984.94 699.06 786.1 242.8 549.7 257.94 1.904808706 0.034833091 0.07184809 15.9639 MARCKS-like 1 /// similar to MARCKS-related protein (MARCKS-like protein 1) (Macrophage myristoylated alanine-rich C kinase substrate) (Mac-MARCKS) (MacMARCKS) (Brain protein F52) 14326 Marcks11: MARCKS-like 1 1090.15 1065.5 915.39 902.84 654.38 711.6 198.7 505.8 271.67 1.892871561 0.036890646 0.07380764 15.2728 9962 Mbd2: methyl-CpG binding 705.4 147.62 1019.73 112.36 370.48 107.5 65.92 14.24 271.83 3.974764411 0.014285714 0.036 43.8036 domain protein 2 1105 Mea1: male enhanced antigen 1 542.92 668.6 745.81 373.15 443.27 291.3 373 331.2 364.96 1.798256252 0.047787611 0.09168732 11.9939 14305 Mm.10009.3 245.87 217.16 188.38 53.3 153.42 55.43 78.1 79.43 58.1 2.726819875 0.04253112 0.08289765 13.2956 43719 Mm.150985.1 393 518.17 908.05 363.36 370.12 406.2 195.3 152.2 111.3 2.276315543 0.045053869 0.08550767 12.8666 4333 Mm.25004.1 145.84 123.93 76.52 26.6 44.95 15.88 28.28 3.92 34.91 4.481558173 0.037313433 0.07497512 14.8637 9278 Mm.37131.1 290.79 409.6 147.87 153.64 67.38 113.6 173 47.35 77.8 2.681312429 0.035100287 0.07225406 15.847 38596 Mm.45490.1 458.52 300.11 583.52 157.64 158.29 215.6 52.94 334 76.83 2.696759027 0.024193548 0.05605735 21.6519 22096 Mm.69144.1 564.45 289.9 595.48 130.38 120.9 231.2 100.7 88.48 177.73 3.41381462 0.012345679 0.0373251 41.2274 21487 Mm.9772.3 207.88 220.36 148.09 29.05 85.16 103.9 122.9 53.97 65.17 2.504911335 0.04757859 0.0923676 11.7365 8468 Mocs2: molybdenum cofactor 451.72 641.1 548.64 204.64 269.88 172.8 296.6 378.2 132.88 2.256395453 0.02972028 0.06585082 17.5962 synthesis 2 29403 Mrpl9: mitochondrial 687.37 522.93 342.88 378.66 145.59 253.6 220.5 250.8 282.44 2.028206166 0.043112513 0.08283912 13.3899 ribosomal protein L9 6034 Mrps23: mitochondrial 189.41 237.99 295.52 122.32 119.68 82.57 55.82 57.01 56.99 2.924492809 0.035310734 0.07228343 15.7753 ribosomal protein S23 44561 Mrps23: mitochondrial 133.78 165.37 174.49 82.76 82.15 57.97 48.91 9.82 35.54 2.986851647 0.048430493 0.09099851 12.1046 ribosomal protein S23 18672 Mt4: metallothionein 4 471.49 401.25 465.5 283.03 160.15 374.6 77.11 182.5 150.05 2.180449535 0.037926675 0.07498946 14.9389 8584 Mtap: methylthioadenosine 301.33 399.52 615.48 133.87 304.21 110.8 88.98 14.43 153.22 3.268395635 0.025559105 0.05434505 23.2205 phosphorylase 3549 Mthfd2: 983.54 1203.2 1182.24 590.25 760.27 536.8 554.4 527.2 690.45 1.841304716 0.02661597 0.06293409 18.3588 methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase 27588 Mxd1: MAX dimerization 993.73 911.74 644.1 466.93 617.29 512.7 418 374.6 279.54 1.910455702 0.029255319 0.06550827 17.6984 protein 1 6161 Mxd1: MAX dimerization 181.67 333.48 504.31 168.5 123.99 172.7 110.9 62.78 111.84 2.716133587 0.029462738 0.06636049 17.5011 protein 1 20325 Myo5b: myosin Vb 768.64 656.09 488.09 409.12 389.77 359 270.7 380 263.4 1.84641373 0.044616877 0.08649855 12.7532 29664 Myom2: myomesin 2 1192.6 1602.7 1540.02 1131.7 1059.7 972 571.8 941.8 785.78 1.587230631 0.043340381 0.082537 13.4485 28881 Nalp4f: NACHT, leucine rich 2150.11 2492.3 2718.12 1515.2 1789.6 1160 566.2 1035 625.39 2.199965628 0.010638298 0.03808511 38.9565 repeat and PYD containing 4F 11528 Nalp6: NACHT, leucine rich 317.78 138.89 39.96 17.77 77.33 22.29 55.67 9.16 5.59 5.288642777 0.031695721 0.06955098 16.6649 repeat and PYD containing 6 41896 Nalp9b: NACHT, LRR and 743.42 818.13 815.08 320.66 556.55 474.3 285.5 410.1 285.42 2.037874176 0.026974952 0.06290944 18.4675 PYD containing protein 9b 18033 Ncoa4 /// LOC627557: 552.62 540.61 580.1 250.08 280.29 212.8 299.8 200.4 190.95 2.333403057 0.027108434 0.06128514 18.8762 nuclear receptor coactivator 4 /// similar to nuclear receptor coactivator 4 21797 Ndrg1: N-myc downstream 760.12 747.8 336.89 280.11 487.1 357.4 374.4 244.3 197.19 1.901454324 0.031796502 0.0690938 16.7306 regulated gene 1 4919 Ndr1: N-myc downstream 442.34 476.68 210.38 300.65 162.3 171.9 239.9 189.1 144.37 1.869588969 0.048053024 0.0935156 11.5462 regulated-like 10414 Nefl: neurofilament, light 1726.22 1655.4 1459.28 902.95 1121 600.9 759.2 965.7 548.27 1.976692432 0.022813688 0.05089987 25.2396 polypeptide 2584 Nes: nestin 259.68 196.54 282.1 75.72 199.89 71.08 119.4 87.37 86.2 2.308404202 0.046753247 0.09178066 11.8681 6998 Neurog2: neurogenin 2 231.05 418.13 218.55 123.46 78.36 80.47 63.67 209.6 71.81 2.766114122 0.047928513 0.09439751 11.403 9918 Nobox: NOBOX oogenesis 396.92 408.09 475.01 129.03 371.41 87.59 172.8 98.82 245.05 2.317449397 0.038327526 0.07741773 14.2596 homeobox 17216 Nudcd2: NudC domain 1083.58 1300.2 1922.19 656.24 404.23 762.1 293 236.5 633.56 2.884501117 0.012987013 0.03718615 41.8566 containing 2 2861 Nudcd2: NudC domain 653.94 528.12 803.02 415.16 310.05 389.2 346.4 283.8 405.47 1.846517339 0.047745358 0.09168288 11.986 containing 2 3960 Nupr1: nuclear protein 1 312.62 225.23 176.51 47.1 36.87 54.82 8.86 46.3 100.04 4.859757135 0.018099548 0.04529412 27.5871 3961 Nupr1: nuclear protein 1 208.1 133.13 133.4 11.64 27.13 47.78 1.98 17.52 68.53 5.437392599 0.029982363 0.06595532 17.6434 2981 Oas1c: 2′-5′ oligoadenylate 1384.52 1483.8 1747.71 600.25 1009 720.6 552.8 343.8 414.35 2.535773144 0.00990099 0.03722772 37.9655 synthetase 1C 1142 Oas1d /// Oas1e: 2′-5′ 2035.81 1982.1 2708.21 777.35 1074.7 732.5 695 757.1 651.09 2.869641642 0 0.02992754 53.6191 oligoadenylate synthetase 1D /// 2′-5′ oligoadenylate synthetase 1E 19318 Obfc2b: oligonucleotide/oligosaccharide- 433.1 115.04 679.94 161.64 146 98.16 107.4 78.98 143.91 3.336675225 0.020512821 0.04188034 29.5008 binding fold containing 2B 10199 Odf2: outer dense fiber of 1037.05 1156.3 1111.85 662.64 858.1 614 392.7 651.3 460.77 1.816309428 0.035 0.0724 15.828 sperm tails 2 22813 Osbp2: oxysterol binding 269.05 335.57 568.18 144.89 117.87 130.8 68.72 106.4 53.36 3.771121722 0.016666667 0.04731944 26.6072 protein 2 43535 Pak7: P21 (CDKN1A)- 394.46 1077 817.61 505.83 477.53 544 153 241.8 217.14 2.13996971 0.027322404 0.06455373 17.9674 activated kinase 7 41333 Paqr5: progestin and adipoQ 724.43 758.22 613.93 502.88 471.52 563.1 113.6 175.4 120.97 2.153154125 0.032102729 0.06917603 16.7783 receptor family member V 849 Pdlim1: PDZ and LIM domain 300.99 412.46 570 141.35 241.6 138.6 163.9 202.1 181.18 2.402069959 0.033923304 0.07121436 16.0941 1 (elfin) 41503 Pex10 /// LOC668173 /// 280.61 206.54 96.17 72.22 80.02 54.72 83.5 24.39 29.12 3.391691136 0.028776978 0.06503597 17.8229 LOC671348: peroxisome biogenesis factor 10 /// similar to peroxisome biogenesis factor 10 isoform 1 /// similar to Peroxisome assembly protein 10 (Peroxin-10) (Peroxisome biogenesis factor 10) (RING finger protein 69) 12239 Pgam5: phosphoglycerate 110.6 127.3 151.21 91.12 15.55 11.93 56.81 11.64 29.05 3.601203147 0.046956522 0.09189855 11.8815 mutase family member 5 6474 Phkg1: phosphorylase kinase 178.41 106.98 171.74 40.05 80.47 88.56 39.25 46.03 40.22 2.732560225 0.04787234 0.09175532 11.9989 gamma 1 4052 Pitpnm2: phosphatidylinositol 84.85 63.94 331.06 11.48 54.66 9.66 23.36 16.57 16.8 7.24137931 0.046918123 0.08945109 12.2952 transfer protein, membrane- associated 2 19362 Plac8: placenta-specific 8 662.3 661.38 795.38 468 575.56 338.1 183 196.8 196.89 2.164105864 0.033823529 0.07121569 16.08 20205 Plec1 /// LOC671535: plectin 121.35 70.86 157.14 22.86 52.58 29.9 14.04 42.18 35.14 3.552109812 0.047738693 0.09283082 11.6437 1 /// similar to poly (ADP- ribose) polymerase family, member 10 27915 Plekhg1: pleckstrin homology 1853.45 1666.1 1893.1 1079.7 1334.2 984 491.4 722.9 597.2 2.078008684 0.015873016 0.0412522 29.9928 domain containing, family G (with RhoGef domain) member 1 11164 Plk2: polo-like kinase 2 498.11 383.42 423.89 177.35 110.99 143.6 134.9 38.56 65.38 3.89207078 0.016949153 0.03774011 35.7785 (Drosophila) 15242 Pofut2: protein O- 1778.06 1154.3 2374.19 882.1 1201.9 822.3 491.1 875.2 1214.3 1.934223068 0.02484472 0.05419255 23.0226 fucosyltransferase 2 14202 Pofut2: protein O- 841.36 629.59 1545.03 432.55 580.35 395.1 328.1 451.2 735.19 2.064043252 0.042842215 0.08301289 13.3317 fucosyltransferase 2 10997 Pold3: polymerase (DNA- 1231.65 1183.2 1391.33 824.72 900.21 640.4 329.6 569.7 526.55 2.007913041 0.023980815 0.05843325 20.4291 directed), delta 3, accessory subunit 34590 Pold3: polymerase (DNA- 423.34 669.16 843.98 290.44 334.78 246.5 303.9 237.9 260.63 2.313402702 0.024523161 0.05544959 21.8711 directed), delta 3, accessory subunit 38961 Ppp1r3d: protein phosphatase 575.14 503.37 526.53 166.64 221.68 213.9 94.06 104 89.52 3.607723257 0.009615385 0.03676282 37.8147 1, regulatory subunit 3D 36182 Ppp4c: protein phosphatase 4, 571.66 453.52 340.78 131.19 406.4 205.3 175.5 111.2 158.93 2.298802602 0.035050072 0.07244158 15.8315 catalytic subunit 14726 Prdx1: peroxiredoxin 1 2781.18 3417.9 3506.42 2190.9 2626.8 2285 1226 1574 1195.6 1.749054555 0.017094017 0.04625356 26.9776 14063 Prdx1: peroxiredoxin 1 2078.16 2456.5 2879.78 1833.6 1734.2 1642 870.6 902.3 801.35 1.904999994 0.022088353 0.04886212 26.0918 13692 Prdx1: peroxiredoxin 1 1982.74 2435.2 2494.71 1597.2 1890.1 1553 859.4 1144 886.29 1.743495 0.023460411 0.05467253 22.4906 295 Prdx1: peroxiredoxin 1 687.71 1005.3 1004.39 538.28 643.24 491.2 434.4 689.3 439.9 1.666929311 0.041019956 0.08053954 13.8032 12996 Prdx2: peroxiredoxin 2 2137.92 1606.1 1921.64 1079.9 1587.9 1273 690.7 1588 625.66 1.655379356 0.037457435 0.07846008 14.0576 2801 Prdx2: peroxiredoxin 2 3503.34 3323.1 3762.91 2292.1 2644.3 1942 2586 2530 2441.4 1.467059107 0.041800643 0.08119328 13.6017 42136 Prmt3: protein arginine N- 165 52.27 96.5 11.63 3.78 14.62 15.11 34.44 6.54 7.286809104 0.035302594 0.07236792 15.8727 methyltransferase 3 2615 Prss8: protease, serine, 8 471.01 140.12 249.79 75.51 130.38 26.33 79.43 130.7 70.09 3.36008118 0.029151943 0.06553592 17.6734 (prostasin) 8719 Pstpip1: proline-serine- 44.1 110.11 91.14 10.97 19.4 25.08 18.91 12.49 10.27 5.052512356 0.047161572 0.09181659 11.9108 threonine phosphatase- interacting protein 1 43158 Ptdss2: phosphatidylserine 1203.34 418.9 557.48 508.13 304.61 307.9 188.3 147 386.5 2.366084658 0.046685341 0.08895425 12.3985 synthase 2 41102 Rab3gap1: RAB3 GTPase 460.17 347.13 470.57 199.81 233.06 254.1 132.1 145 138.52 2.317921277 0.026266417 0.06385866 18.2065 activating protein subunit 1 16961 Rap2b: RAP2B, member of 808.09 565.99 369.3 354.3 287.58 166.3 57.48 218.1 87 2.978227632 0.018604651 0.04384496 28.1739 RAS oncogene family 8013 Rasl11b: RAS-like, family 11, 426.89 253.01 172 67.51 155.36 83.97 28.63 67.32 76.13 3.557587906 0.022988506 0.0580613 20.1914 member B 16931 Rassf1: Ras association 551.69 251.68 515.62 171.98 181.71 219.6 213.6 114.1 183.5 2.432506201 0.024767802 0.05414861 23.0186 (RalGDS/AF-6) domain family 1 6797 Rassf5: Ras association 720.77 665.14 560.86 336.47 286.71 262.6 254.6 257.9 267.99 2.336764273 0.022099448 0.05517495 22.0115 (RalGDS/AF-6) domain family 5 19264 Rbm7: RNA binding motif 1311.84 1104.7 1399.09 852.61 1194.9 761.2 564.4 793.3 454.85 1.651371739 0.044444444 0.08668921 12.7196 protein 7 30077 Rbpsuh: Recombining binding 229.78 181.62 164.15 47.11 63.14 54.63 33.26 159.1 37.35 2.917131272 0.047963801 0.09049472 12.1646 protein suppressor of hairless (Drosophila) 17285 Rdh11: retinol dehydrogenase 266.28 352.96 301.12 131.17 93.27 93.1 130.5 206.4 92.85 2.463127752 0.039370079 0.07937008 13.9553 11 3831 Rela: v-rel 1165.05 845.26 817.64 573.79 604.68 707 323.3 379.4 435.95 1.870281638 0.047038328 0.09183798 11.8894 reticuloendotheliosis viral oncogene homolog A (avian) 19286 Rexo2: REX2, RNA exonuclease 2 homolog (S. cerevisiae) 496.13 531.04 541.91 329.27 450.19 238 210.9 214.8 230.19 1.875420574 0.048006509 0.09429889 11.4137 3543 Rgs2: regulator of G-protein 982.72 955.41 1090.21 552.53 601.28 456.3 215.4 392.9 290.79 2.413808495 0.018181818 0.04524242 27.6143 signaling 2 3542 Rgs2: regulator of G-protein 755.61 753.62 945.56 289.77 380.15 277.6 309.3 389.5 287.36 2.539035188 0.022140221 0.05134071 24.8558 signaling 2 38623 Rgs2: regulator of G-protein 439.17 401.76 570.74 252.29 232.03 224.9 47.94 265.8 134.38 2.439549995 0.035714286 0.07222222 15.7414 signaling 2 40641 Rnd1: Rho family GTPase 1 341.36 140.63 50.42 22.78 40.06 50.85 49.94 22.23 23.68 5.081702778 0.031862745 0.06855664 16.9255 996 Rnd3: Rho family GTPase 3 236.49 269.23 240.29 57.64 90.84 104.7 34.95 86.4 66.49 3.383342026 0.027196653 0.06002789 19.3316 995 Rnd3: Rho family GTPase 3 346.48 273.15 396.01 104.43 242.51 112.8 134.1 41.05 157.66 2.563194024 0.031897927 0.06903775 16.7571 44629 Rnf185: Ring finger protein 3391.02 3265.6 3308.22 2163.5 2326.9 1837 1543 1821 2169 1.680373212 0.022222222 0.05532407 22.0213 185 19135 Rnf185: ring finger protein 3100.72 2881.4 3164.78 1942 2217.8 1890 2233 2234 2296.7 1.427717853 0.047833935 0.09054753 12.1523 185 19484 Sc5d: sterol-C5-desaturase 156.19 125.87 470.87 12.69 92.23 44.12 37.46 10.13 75.32 5.53726788 0.026768642 0.06290631 18.417 (fungal ERG3, delta-5-desaturase) homolog (S. cerevisae) 21214 Scarb2: scavenger receptor 412.98 136.41 11.58 17.91 8.27 79.58 23.24 12.15 32.61 6.456837017 0.048995984 0.09481928 11.3271 class B, member 2 14524 Sdhc: succinate 655.46 629.8 569.58 133.4 248.7 128 367.2 95.09 439.58 2.627289338 0.023715415 0.05048748 25.7165 dehydrogenase complex, subunit C, integral membrane protein 16404 Sh3bp2: SH3-domain binding 939.44 869.33 963.81 543.92 577.31 563.7 456.3 460.2 392.82 1.851886733 0.036885246 0.0731102 15.5576 protein 2 11436 Six1: sine oculis-related 890.55 896.49 591.29 257.89 404.29 126.8 116.8 139.6 145.28 3.995178901 0 0.02714286 66.8915 homeobox 1 homolog (Drosophila) 16644 Slc20a1: solute carrier family 755.61 816.13 1040.94 591.52 587.71 537.5 338.8 299.8 249.93 2.00568847 0.036745407 0.07408136 15.2304 20, member 1 5126 Slc25a15: solute carrier 2097.82 2285.9 2519.54 1552.6 1649.2 1444 801.2 1031 1205.9 1.796727072 0.024657534 0.05515982 21.9246 family 25 (mitochondrial carrier ornithine transporter), member 15 42635 Slc7a14: Solute carrier family 850.08 861.15 971.47 367.62 635.72 604.9 171.7 384 263.26 2.210530653 0.024213075 0.05830508 20.4881 7 (cationic amino acid transporter, y+ system), member 14 15341 Slc9a3r1: solute carrier family 1945.59 1874.9 1042.14 1213.4 1279.4 924.9 732.2 1247 905.41 1.543013175 0.04248366 0.08125999 13.6676 9 (sodium/hydrogen exchanger), isoform 3 regulator 1 15340 Slc9a3r1: solute carrier family 1511.18 1791 882.39 908.38 1070.8 773.7 603.5 1141 742.49 1.597206796 0.04744186 0.08977984 12.3407 9 (sodium/hydrogen exchanger), isoform 3 regulator 1 29662 Slco4a1: solute carrier organic 1518.9 1099.7 758.84 781.47 590.77 472.9 410.2 560.3 482.97 2.047771782 0.023752969 0.05806809 20.3739 anion transporter family, member 4a1 22832 Smurf1 /// LOC640390: 353.27 405.72 431.46 185.4 183.4 173.3 130.3 182.9 293.86 2.071951336 0.04549763 0.08836651 12.5257 SMAD specific E3 ubiquitin protein ligase 1 /// similar to Smad ubiquitination regulatory factor 1 (Ubiquitin- protein ligase SMURF1) (Smad-specific E3 ubiquitin ligase 1) (hSMURF1) 7515 Snap29: synaptosomal- 1533.29 1209.3 1300.59 1097.4 921.79 856.9 676.1 678.9 687.34 1.644127897 0.047818792 0.09289989 11.6499 associated protein 15156 Snord22: small nucleolar 244.55 88.91 292.33 138.36 78.77 71.21 96.16 68.67 49.02 2.492243971 0.041755889 0.08124197 13.5908 RNA, C/D box 22 10772 Snrpb2: U2 small nuclear 1280 1540.4 1365.87 675.42 748.01 668.4 399.1 607.5 397.8 2.394785166 0.013513514 0.03754505 33.014 ribonucleoprotein B 20449 Snrpb2: U2 small nuclear 1101.45 1113.1 1328.87 444.18 372.6 458.6 607.3 424.6 345.21 2.67191229 0.016260163 0.03837398 35.0616 ribonucleoprotein B 1262 Sox2: SRY-box containing 258.38 397.22 227.54 100.5 112.85 106.8 94.1 81.95 80.38 3.06347995 0.032307692 0.07045128 16.4379 gene 2 7733 Srd5a2l: steroid 5 alpha- 951.51 803.16 917.18 539.46 538.83 573.3 345.4 553.4 479.19 1.763841853 0.042576419 0.08121543 13.679 reductase 2-like 37863 Ssr3: signal sequence 878.88 551.79 1339.32 496.85 533.72 503.9 432 471.5 368.38 1.974066235 0.036986301 0.07271233 15.6044 receptor, gamma 17274 St3gal5: ST3 beta-galactoside 585.5 294.61 591.89 101.96 252.48 156 129.7 214.2 153.36 2.921765366 0.015037594 0.03827068 34.2305 alpha-2,3-sialyltransferase 5 10512 Stat6: signal transducer and 280.93 369.43 537.91 177.71 247.51 140.3 74.96 158.2 163.26 2.470544207 0.038560411 0.07460154 15.0996 activator of transcription 6 5687 Surf5: surfeit gene 5 808.83 625.57 901.86 425.58 600.45 367.5 196.1 219.1 363.82 2.150727493 0.024630542 0.05834154 20.6282 16783 Taf13: TAF13 RNA 2786.83 2273 2785.38 1860.7 2037.4 1751 1700 1367 1418.5 1.548259965 0.030769231 0.06631909 17.421 polymerase II, TATA box binding protein (TBP)- associated factor 14515 Taok3: TAO kinase 3 840.36 751.13 664 644.14 406.28 520.9 288.5 201 341.2 1.877923992 0.042726348 0.08343845 13.1523 21642 Tax1bp3 /// Rpl13: Tax1 871.73 903.94 1048.44 382.12 394.43 282.3 507.1 145.2 438.71 2.627237926 0.016666667 0.04101852 30.5599 (human T-cell leukemia virus type I) binding protein 3 /// ribosomal protein L13 502 Taz: tafazzin 510.91 478.79 738.95 285.8 194.27 193.5 116.3 261.3 97.64 3.009750152 0.023529412 0.05086275 25.5673 6617 Tcl1: T-cell lymphoma 4221.74 3745.3 4210.23 2520.7 3350.8 3381 2300 2780 3125.2 1.394976158 0.044399596 0.08380424 13.0961 breakpoint 1 19537 Thedc1: thioesterase domain 749.49 760.8 818.91 422.7 601.57 400.7 231.5 336.5 417.73 1.932376769 0.036599764 0.07688705 14.4348 containing 1 20152 Thrap3: thyroid hormone 308.4 324.33 307.94 159.33 140.04 211.4 90.03 100.2 151.4 2.207264707 0.048242028 0.09426547 11.4399 receptor associated protein 3 16803 Tle6: transducin-like enhancer 1270.14 833.99 1229.7 374.24 654.97 691.3 407.2 562.4 495.75 2.092904854 0.017241379 0.04622126 27.0809 of split 6, homolog of Drosophila E(spl) 15195 Tm2d2: TM2 domain 934.68 572.01 641.41 527.63 320.67 388.1 290.4 286.3 252.38 2.079960494 0.041896362 0.08087468 13.7569 containing 2 21204 Tmed10 /// LOC634748: 371.69 689.99 932.01 227.36 344.45 312 356.4 335.3 331.6 2.090851887 0.029307282 0.06547661 17.7043 transmembrane emp24-like trafficking protein 10 (yeast) /// similar to transmembrane trafficking protein 15880 Tmed10 /// LOC634748: 293.24 526.59 744.83 183.86 260.8 259 306.9 282.8 262.97 2.01075635 0.042769857 0.08350984 13.1531 transmembrane emp24-like trafficking protein 10 (yeast) /// similar to transmembrane trafficking protein 15864 Tmed10 /// LOC634748: 325.23 522.46 807.94 214.86 292.41 263.9 328.4 287.9 276.07 1.990478194 0.048141892 0.09307995 11.6733 transmembrane emp24-like trafficking protein 10 (yeast) /// similar to transmembrane trafficking protein 21746 Tmem109: transmembrane 658.76 639.21 690.17 367.58 528.21 245.5 273.8 272.9 273.33 2.027348928 0.036 0.07345778 15.3724 protein 109 14887 Tmem109: transmembrane 827.27 787.55 910.96 487.81 701.24 347.9 350.2 365 381.93 1.917784713 0.037974684 0.07493671 14.9506 protein 109 8336 Tmem38a: transmembrane 965.95 199.02 508.25 119.7 369.44 96.15 251.5 101.5 150.48 3.073850902 0.024561404 0.05080702 24.4359 protein 38a 10674 Tor1a: torsin family 1, member A (torsin A) 1760.16 1607.9 1566.85 1294.5 1207 1120 851.9 880.3 816.44 1.599693348 0.047144152 0.09024781 12.187 7470 Tpbg: trophoblast 135.67 173.87 65.62 38.44 9.01 28.02 6.79 31.8 103.96 3.441519127 0.047454702 0.0919931 11.8366 glycoprotein 20812 Tpi1: triosephosphate 723.43 510.71 278.29 243.4 202.66 199.6 498.9 79.81 92.94 2.29629236 0.03686088 0.07673801 14.4886 isomerase 1 22085 Transcribed locus 244.72 168.35 553.92 235.2 92.48 72.5 7.42 50.24 1 4.21493331 0.035410765 0.07242682 15.7775 43618 Transcribed locus 1331.08 1132.8 759.97 700.03 776.17 653.8 600.2 448.6 142.5 1.941371472 0.0390625 0.07442274 15.175 30279 Transcribed locus 115.59 77.5 3.01 1 6.1 4.39 6.91 7.21 3.07 13.67503487 0.042162162 0.08108468 13.6466 31948 Transcribed locus 948.04 695.42 1011.76 481.07 569.52 551.4 635.4 513.4 462.89 1.652432858 0.046961326 0.08948742 12.2985 36521 Transcribed locus 163.5 288.96 275.95 153.58 132.29 129 127.8 62.86 77.98 2.131349485 0.049114332 0.094635 11.3498 14557 Transcribed locus, moderately 389.93 446.02 354.24 146.9 73.38 178.6 150.5 243.5 285.69 2.207018682 0.045135406 0.0843096 13.0436 similar to XP_574723.1 PREDICTED: similar to LRRGT00097 [Rattus norvegicus] 31203 Transcribed locus, weakly 833.28 557.28 868.7 344.25 284.45 400.2 464.4 244.1 342.7 2.172271392 0.022727273 0.05269481 23.5482 similar to XP_417295.1 PREDICTED: similar to TAF3 protein [Gallus gallus] 16554 Trfp: Trf (TATA binding 1346.13 1510.8 1419.34 707.69 420.35 502.5 668.7 1297 686.12 1.997305029 0.023323615 0.0545967 22.442 protein-related factor)- proximal protein homolog (Drosophila) 11566 Trip11: thyroid hormone 259.32 592.74 496.79 341.11 199.04 280 193.4 155.1 127.48 2.081494398 0.037878788 0.07494108 14.9376 receptor interactor 11 39305 Troap: trophinin associated 208.07 262.5 390.33 82.47 98.83 71.69 101.3 44.16 107.74 3.401287978 0.025114155 0.0585312 20.0849 protein 8651 Trpc2: transient receptor 1159.04 683.82 924.49 504.31 574.63 394.4 398.4 456.4 182.58 2.204436195 0.02359882 0.05485742 22.5014 potential cation channel, subfamily C, member 2 17247 Ttk: Ttk protein kinase 442.51 328.09 595.94 156.99 233.89 156.6 291.1 218.8 142.18 2.278383087 0.037859008 0.07429939 15.191 20704 Tubb2b: tubulin, beta 2b 2089.18 1881.4 2187.75 1223.2 1598.2 1370 901.7 1304 685.75 1.739163956 0.02832244 0.06042847 19.5561 1904 Ube2a: ubiquitin-conjugating 668.24 817.55 665.53 322.75 424.91 331.9 208 371.1 379.5 2.110968831 0.036401099 0.07271978 15.6237 enzyme E2A, RAD6 homolog (S. cerevisiae) 6873 Ube2i /// LOC546265 /// 881.06 714.36 770.75 667.98 572.39 299.1 178.7 412.2 456.5 1.829369083 0.049193548 0.09460215 11.3561 LOC669417: ubiquitin- conjugating enzyme E2I /// similar to Chain A, Human Ubiquitin-Conjugating Enzyme Ubc9 /// similar to Ubiquitin-conjugating enzyme E2 I (Ubiquitin-protein ligase I) (Ubiquitin carrier protein I) (SUMO-1-protein ligase) (SUMO-1-conjugating enzyme) (Ubiquitin- conjugating enzyme UbcE2A) 34066 Ube2w: ubiquitin-conjugating 257.73 223.92 304.28 83.65 208.87 56.27 64.14 66.41 62.1 2.903110225 0.032258065 0.07035842 16.4371 enzyme E2W (putative) 30305 Umodl1: uromodulin-like 1 918.71 1173.2 1195.72 468.99 479.34 394.6 140.4 315.4 169.66 3.340415155 0 0.02952381 59.0622 27170 Unc5a: unc-5 homolog A (C. elegans) 251.93 17.43 149.64 24.49 31.01 22.93 71.25 19.8 14.94 4.543975708 0.036948749 0.07631307 14.5235 18877 Vil2: villin 2 241.97 205.21 109.2 76.45 75.17 88.63 56.94 39.13 59.75 2.809503371 0.038596491 0.07755945 14.307 36640 Wdr27: WD repeat domain 27 258.28 184.34 219.19 117.86 87.15 48.94 74.51 75.45 48.47 2.925903002 0.0375 0.07488333 14.8953 40438 Wdr40b: WD repeat domain 412.95 601.38 440.4 258.01 180.34 165.1 177.8 333.6 44.28 2.509864477 0.034023669 0.07133136 16.1014 40B 20216 Wdr82: WD repeat domain 930.14 666.97 795.89 478.36 548.79 548.8 439.9 334.8 377.74 1.754141621 0.047417443 0.09220999 11.7317 containing 82 44710 Wfdc3: WAP four-disulfide 840.41 352.61 513.04 317.4 228.96 204.5 83.53 153.4 181.23 2.918761708 0.024647887 0.0509507 24.4457 core domain 3 4516 Xlr3a /// Xlr3b /// 360.83 588.71 622.92 230.28 410.11 221.9 206 332.5 245.03 1.910945836 0.036817102 0.07669438 14.4846 MGC76689: X-linked lymphocyte-regulated 3A /// X

linked lymphocyte-regulated 3B /// hypothetical protein LOC574437 6776 Xmr /// LOC546272 /// 402.45 431.9 419.31 132.31 243.77 319 93.22 113 120.66 2.453418398 0.029411765 0.06629181 17.4967 LOC619991 /// LOC664810 /// LOC664861 /// LOC664877 /// LOC664890 /// LOC664906 /// LOC664923 /// LOC664944 /// LOC664989: Xmr protein /// similar to Xlr-related, meiosis regulated /// similar to Xlr-related, meiosis regulated /// similar to Synaptonemal complex protein 3 (SCP-3) /// similar to Xlr-related, meiosis regulated /// similar to Xlr- related, meiosis regulated /// similar to Xlr-related, meiosis regulated /// similar to Xlr- related, meiosis regulated /// similar to Xlr-related, meiosis regulated /// similar to Xlr- related, meiosis regulated /// similar to Xlr-related, meiosis regulated 6777 Xmr /// LOC546272 /// 416.14 408.25 408.94 135.94 270.28 290.5 105.7 134.5 133.3 2.304945055 0.038860104 0.0744905 15.1475 LOC619991 /// LOC664810 /// LOC664861 /// LOC664877 /// LOC664890 /// LOC664906 /// LOC664923 /// LOC664944 /// LOC664989: Xmr protein /// similar to Xlr-related, meiosis regulated /// similar to Xlr-related, meiosis regulated /// similar to Synaptonemal complex protein 3 (SCP-3) /// similar to Xlr-related, meiosis regulated /// similar to Xlr- related, meiosis regulated /// similar to Xlr-related, meiosis regulated /// similar to Xlr- related, meiosis regulated /// similar to Xlr-related, meiosis regulated /// similar to Xlr- related, meiosis regulated /// similar to Xlr-related, meiosis regulated 15133 Ywhaq: tyrosine 3- 823.51 1230.4 1166.2 689.41 787.92 682.6 668.7 504.4 743.91 1.579678045 0.048561151 0.09080635 12.127 monooxygenase/tryptophan 5- monooxygenase activation protein, theta polypeptide 14866 Ywhaz: tyrosine 3- 1349.62 789.35 427.74 385.13 670.02 394.3 284.5 439.5 466.58 1.944403621 0.048956661 0.09480203 11.319 monooxygenase/tryptophan 5- monooxygenase activation protein, zeta polypeptide 27398 Zar1: zygote arrest 1 308.67 302.35 296.84 96.91 62.32 61.6 36.14 73.34 105 4.17109646 0.016853933 0.04059925 30.8299 8460 Zfp219: zinc finger protein 362.85 474.33 421.09 139.56 154.27 248.9 222.6 276.2 128.61 2.150613169 0.041622199 0.08153682 13.5586 219 15729 Zfp36l2: zinc finger protein 1493.92 1568.6 1661.69 1083.2 1187.2 1122 833.5 1041 686.1 1.587178186 0.047877145 0.09053899 12.154 36, C3H type-like 2 20879 Zfp422-rs1: zinc finger 807.14 637.1 963.93 639.73 531.32 551.3 241.2 450.1 320.33 1.761665271 0.049153908 0.09463336 11.3527 protein 422, related sequence 1 24731 Zfp444: zinc finger protein 153.25 73.77 591 9.86 2.23 35.58 45.91 75.68 121.03 5.63588136 0.041202673 0.08044915 13.8348 444 7994 Zfp503: zinc finger protein 499.68 1344.6 631.84 248.83 28.76 97.85 46.17 549 78.64 4.71964318 0.02 0.036 49.7065 503 7995 Zfp503: zinc finger protein 201.34 138.04 36.43 20 36.65 32.65 17.34 48.18 62.9 3.452232225 0.04757548 0.08988411 12.2507 503 44691 Zfp68: zinc finger protein 68 836.97 770.67 353.93 367.82 511.34 379.8 260.4 345.8 315.87 1.798780376 0.037125749 0.07644311 14.5373 8911 Zfp71-rs1: zinc finger protein 118.31 304.51 288.84 100.79 115.62 155.5 55.72 138.6 55.13 2.290505311 0.043478261 0.08252033 13.4658 71, related sequence 1 17202 Zfp90: zinc finger protein 90 148.51 168.8 284.96 41.22 44.14 22.58 38.95 17.6 56.83 5.442526658 0.024539877 0.05421268 22.8885 1832 Zmat2: zinc finger, matrin 271.97 245.47 570.3 68.8 63.18 133.6 110.3 99.83 40.13 4.218008376 0.023972603 0.05133562 24.0851 type 2

indicates data missing or illegible when filed

TABLE 8B Oct. Oct. Oct. Row Gene 04, 2001 04, 2002 04, 2003 NI.1.1 NI.1.2 NI.1.3 NI.2.1 NI.2.2 NI.2.3 foldchange fdr t. pvals 52 transferrin receptor 624.69 241.34 260.79 1658.5 1221.5 1475.4 2092.35 1394.63 2043.46 0.227967388 0 0.00015951 154 eukaryotic translation initiation 1574.05 898.06 884.18 3064.3 2464.01 3091 3612.17 2968.05 3465.95 0.359626325 0 0.00015921 factor 3, subunit 8 785 transmembrane emp24 protein 158.97 64.18 182.56 508.83 418.62 577.06 745.64 731.85 729.56 0.218619664 0 0.00022179 transport domain containing 6 1785 cathepsin B 725.96 401.03 413.68 1480.9 1297.15 1599.4 2070.39 1870.47 2628.6 0.28148163 0 0.00024093 4369 ATP-binding cassette, sub- 415.1 244.32 320.89 937.07 895.73 1089.7 1088.85 1163.3 2060.89 0.270972664 0 0.0003167 family F (GCN20), member 1 4798 junction-mediating and 143.62 100.64 83.34 547.49 231.34 463.45 532.88 603.44 674.49 0.214602255 0 0.00036372 regulatory protein 4799 junction-mediating and 290.52 233.15 287.38 1194 1060.93 1111.5 1676.86 1290.77 1588.17 0.204752955 0 6.13E−006 regulatory protein 5181 acylphosphatase 1, erythrocyte (common) type 16.91 108.49 111.19 532.02 571.18 559.42 528.01 477.38 466.65 0.15095098 0 0.00038783 7126 transferrin receptor 689.39 491.5 251.38 1428.2 1227.04 1221.1 2091.98 1833.64 2227.85 0.285602903 0 0.00068689 10805 RIKEN cDNA 9130011J15 285.53 256.11 271.55 782.98 735.67 749.47 1214.59 1679.66 1121.66 0.258811622 0 0.0002899 gene 10887 phosphatidylserine synthase 2 708.39 150.51 190.22 1424.2 1092.46 1221.8 1035.72 1127.98 1999.15 0.265555293 0 0.00127543 12367 Kruppel-like factor 9 42.96 50.16 156.96 413.31 485.3 353.82 523.55 415.15 759.55 0.16950669 0 0.00019734 13878 general transcription factor IIIC, 27.87 16.57 35.71 474.48 220.1 217.44 516.42 384.03 566.54 0.067380969 0 2.35E−005 polypeptide 4 13972 eukaryotic translation initiation 203.48 187.05 266.56 1013.4 919.72 998.66 1287.5 1098.19 1049.17 0.206416571 0 1.86E−006 factor 3, subunit 6 14002 phosphatidylserine synthase 2 602.84 152.26 203.21 1152.7 870.06 1008.7 1052.55 1114.61 1781.74 0.274571264 0 0.00102264 14683 diacylglycerol kinase, epsilon 190.03 434.95 115.62 1081.8 777.24 733.1 1097.92 905.2 997.74 0.264831986 0 0.00044972 15504 torsin family 2, member A 231.7 99.13 132.44 803.51 625.23 692.06 515.53 1579.92 860.9 0.182492146 0 0.00031663 15713 acylphosphatase 1, erythrocyte (common) type 9.09 70.55 99.27 431.09 432.79 469.83 452.15 386.11 368.38 0.140854607 0 0.00068273 15791 eukaryotic translation initiation 117.88 107.21 148.87 614.35 581.81 595.12 849.71 634.84 809.58 0.183070977 0 2.91E−006 factor 3, subunit 6 18122 acylphosphatase 1, erythrocyte (common) type 24.1 104.37 109.38 657.52 691.59 706.49 594.96 581.28 463.27 0.12873771 0 0.00010853 18375 solute carrier family 19 227.44 127.66 156.95 731.75 478.33 711.17 1052.97 795.48 1291.81 0.202330925 0 0.0001809 (sodium/hydrogen exchanger), member 3 19172 transmembrane protein 111 330.63 240.26 230.31 1271.5 949.26 808.68 1152.76 998.66 1763.99 0.230733122 0 7.44E−005 21863 Kruppel-like factor 9 126.03 324.94 264.78 1413.6 1073.94 1024.2 1693.05 992.37 1695.4 0.181373344 0 8.56E−005 21873 eukaryotic translation initiation 688.45 338.22 292.12 1367.9 940 1082 1811.77 1859.33 2228.32 0.283934988 0 0.00112513 factor 3, subunit 8 22149 phosphatidylserine synthase 2 1200.27 227.6 292.55 2416.8 1921.95 2063.5 1639.91 1905.6 3229.72 0.261113788 0 0.00137219 22419 eukaryotic translation initiation 253.42 148.89 203.42 867.23 627.04 653.69 1252.51 944.86 908.52 0.23058519 0 7.39E−005 factor 3, subunit 6 27213 DNA segment, Chr 19, Brigham 566.7 267.24 1036.42 1513.8 1212.97 2166.7 2823.83 2513.75 3203.16 0.278448166 0 0.00268403 & Women's Genetics 1357 expressed 28204 galactosidase, beta 1 426.39 169.6 51.27 1713.4 1707.87 1919 2551.5 2521.75 2747.95 0.098357318 0 0.00014849 28632 ankyrin repeat domain 38 29.64 6.72 16.18 346.3 291.12 247.57 166 148.99 316.27 0.069302556 0 4.02E−005 29867 RIKEN cDNA 4933433K01 145.78 41.38 31.11 448.82 321.98 385.46 480.01 555.13 902.54 0.141095173 0 0.00031856 gene 33396 Transcribed locus 352.3 82.9 105.87 670.9 481.47 592.69 1401.57 1113.63 1247.74 0.196466957 0 0.00143556 41050 RIKEN cDNA 4930427A07 225.06 114.11 217.2 462.21 493.17 756.34 822.19 1212.27 977.74 0.23555437 0 0.00068706 gene 29064 ubiquitin specific peptidase 22 470.08 134.25 91.36 877.44 673.24 719.13 843.91 842.44 1309.02 0.264260671 0.01064 0.00127129 21759 eukaryotic translation initiation 873.58 406.65 383.89 1537.6 1184.08 1444.6 1689.92 1790.34 2140.93 0.340049716 0.01111 0.00060111 factor 3, subunit 8 22191 ribosomal protein L24 /// similar 1172.49 672.1 952.29 1781.4 1430.15 1946.1 2400.65 2576.5 2545.94 0.441122173 0.01124 0.0018963 to ribosomal protein L24 /// similar to ribosomal protein L24 2935 sirtuin 1 ((silent mating type 159.78 122.53 182.71 551.66 431.36 568.18 612.19 521.34 692.06 0.275421332 0.01136 2.03E−005 information regulation 2, homolog) 1 (S. cerevisiae) 4370 ATP-binding cassette, sub- 427.95 279.01 441.26 1100.4 946.89 1266 1325.41 1128.42 2317.25 0.284061348 0.01136 0.00045761 family F (GCN20), member 1 16122 Transcribed locus 93.98 30.44 15.4 215.29 193.76 209.2 360.32 327.29 349.09 0.168971872 0.01149 0.00047997 153 eukaryotic translation initiation 475.14 206.19 253.03 1108.7 888.34 784.61 1267.74 1026.05 1313.35 0.292501663 0.01163 0.00024627 factor 3, subunit 8 8022 ATP-binding cassette, sub- 152.19 156.91 162.97 363.57 305.96 451.65 884.29 887.81 683.59 0.263957035 0.01163 0.00200161 family F (GCN20), member 2 28457 solute carrier family 30 (zinc 233.42 27.36 61.68 315.4 343.75 619.79 393.91 491.5 503.8 0.241710549 0.01176 0.00194384 transporter), member 1 21824 thioredoxin-like 2 294.52 175.68 266.05 909.58 693.73 804.9 643.13 850.93 762.17 0.315686342 0.0119 4.42E−005 7389 inositol polyphosphate-5- 25.77 21.31 39.99 241.41 177.04 187.24 342.97 181.11 290.47 0.122613079 0.01205 1.28E−005 phosphatase E 16808 cathepsin B 130.23 101.77 67.38 288.01 181.13 261.76 690.28 580.37 717.78 0.22018659 0.0122 0.00427226 39214 1-acylglycerol-3-phosphate O- 499.54 525.47 363.14 1210.6 1108.45 1066.1 1281.2 1561.27 1458.73 0.361200628 0.0125 7.86E−005 acyltransferase 5 (lysophosphatidic acid acyltransferase, epsilon) 3399 abhydrolase domain containing 6 156.99 100 43.52 553.9 326.89 296.3 593.6 167.18 618.84 0.235075546 0.01266 0.00413915 53 transferrin receptor 409.32 206.62 95.99 595.48 591.14 503.44 983.73 948.43 1145.38 0.298653411 0.01316 0.00301392 9791 PQ loop repeat containing 2 13.76 7.56 6.29 292.48 156.56 55.45 60.34 219.02 172.47 0.057742178 0.01333 0.00024888 7125 transferrin receptor 361.01 329.39 377.07 974.9 842.63 895.37 1430.85 1069.76 1417.72 0.321952338 0.01351 0.00011751 14950 eukaryotic translation initiation factor 44.09 7.7 7.32 207.56 115.15 151.62 314.47 175.57 291.88 0.094105473 0.0137 0.00022399 2C, 5 18250 apoptotic peptidase activating 36.46 51.69 50.02 277.53 197.48 388.51 297.58 228.07 287.72 0.164793159 0.01389 8.99E−006 factor 1 10657 jumonji, AT rich interactive 55.24 122.77 112.59 314.35 218.11 459.64 670.73 493.09 411.48 0.226376879 0.01408 0.00075321 domain 1C (Rbp2 like) 43911 gb: BM122336 75.29 12.69 9.34 166.18 32.25 202.06 433.2 516.27 301.93 0.117828669 0.01449 0.00986852 /DB_XREF = gi: 17106104 /DB_XREF = L0508F03-3 /CLONE = L0508F03 /FEA = EST /CNT = 3 /TID = Mm.218397.1 /TIER = ConsEnd /STK = 2 /UG = Mm.218397 /UG_TITLE = ESTs 18703 transcription elongation factor B 231.44 240.04 198.89 638.35 629.15 741.99 859.61 921.16 783.83 0.293116226 0.01471 1.39E−005 (SIII), polypeptide 3 16204 protective protein for beta- 474.09 446.21 267.96 1117.8 569.65 1350.3 1365.1 642.54 1356.92 0.371197851 0.01493 0.00629467 galactosidase 15395 Vacuolar protein sorting 54 714.94 245.49 144.2 1535.2 886.77 1048.1 1134.23 921.8 1216.19 0.327673024 0.01515 0.00227705 (yeast) 4980 sphingosine-1-phosphate 262.03 173.69 51.88 1215.3 589.36 577.14 509.63 536.21 763.86 0.232661338 0.01538 0.0016041 phosphatase 1 54 transferrin receptor 434.35 354.1 332.55 1138.5 818.28 858.07 1238.66 1119.89 1324.05 0.345056322 0.01563 0.00010839 27902 potassium in wardly-rectifying 44.82 139.14 63.27 323.91 232.15 319.5 516.23 473.27 565.17 0.203462224 0.01587 0.00046105 channel, subfamily K, member 6 39802 neuropilin (NRP) and tolloid (TLL)-like 2 87 64.53 146.38 522.51 475.14 750.45 427.95 275.96 347.24 0.212849871 0.01639 0.00032483 384 ribosomal protein S15 256.87 118.98 155.05 330.7 201.23 1135.8 727.25 514.63 1106.92 0.264353593 0.01667 0.01955601 6466

228.12 205.44 238.32 906 787.64 785.29 730.81 656.42 846.69 0.285126834 0.01667 3.78E−006 /DB_XREF = gi: 14010854 /GEN = Usmg3 /FEA = FLmRNA /CNT = 2 /TID = Mm.218588.1 /TIER = FL /STK = 1 /UG = Mm.218588 /LL = 83678 /DEF = Mus musculus upregulated during skeletal muscle growth 3 (Usmg3), mRNA. /PROD = upregulated 34766 Vacuolar protein sorting 33A 315.2 115.51 221.53 607.77 456.63 589.67 807.65 809.12 987.11 0.306363391 0.01667 0.00105604 (yeast) 38885 RNA, U transporter 1 515.79 234.67 214.8 722.54 562.88 810.9 985.1 1105.78 1283.74 0.352868063 0.01681 0.00227145 8821 peptidase (mitochondrial 73.11 56.51 41.28 381.32 318.1 307.73 329.1 251.1 518.94 0.16227585 0.01695 1.65E−005 processing) alpha 10448 RIKEN cDNA 2610028H07 638.95 517.06 757.25 1387 1282.58 1540.6 1558.37 2078.88 1484.02 0.410069668 0.01724 0.00022595 gene 14001 phosphatidylserine synthase 2 252.19 121.81 137.37 847.59 360.31 528.7 764.33 553.32 801.99 0.265216895 0.01724 0.0006063 21527 DEAD (Asp-Glu-Ala-Asp) box 173.52 35.84 59.84 496.4 167.03 182.83 391.02 405.54 415.71 0.26154586 0.01739 0.00468851 polypeptide 49 29344 Adult male cecum cDNA, 90.7 19.1 227.83 613.93 432.25 327.99 562.83 671.26 386.9 0.225450393 0.01754 0.00292411 RIKEN full-length enriched library, clone: 9130409M07 product: hypothetical protein, full insert sequence 13579 RIKEN cDNA 9430010O03 1276.81 930.39 852.58 2128.7 1524.54 2270.8 2042.66 2601.49 3336.82 0.440098756 0.0177 0.00221166 gene 8699 homeodomain interacting 703.08 358.75 437.43 1281.1 954.65 1185.9 1575.69 1648.73 1861.89 0.352435769 0.01786 0.00072822 protein kinase 1 16053 expressed sequence C77815 226.98 68.5 120.21 355.27 288.1 364.69 689.78 629.82 713.08 0.273413709 0.01786 0.00247561 33270 gene model 104, (NCBI) 167.88 96.62 189.61 623.96 423.95 354.11 625.11 416.17 774.69 0.282232077 0.01802 0.00055679 3951 solute carrier family 25, member 196.31 138.07 287.87 552.92 426.31 612.23 716.16 716.8 838.71 0.322148103 0.01818 0.00045152 36 8247 melanocyte proliferating gene 1 38.3 8.3 8.89 124.7 125.7 87.63 225.51 241.69 255.09 0.104666516 0.01835 0.00028537 24977 origin recognition complex, 64.74 3.28 40.64 285.69 259.43 282.71 113.94 217.49 143.37 0.166831717 0.01852 0.00382844 subunit 4-like (S. cerevisiae) 28887 deficient 5, cell division cycle 521.19 337.32 431.77 1405.9 1199.34 1296.8 1001.57 1386.43 1286.19 0.34061178 0.01852 3.87E−005 46 (S. cerevisiae) 44778 gb: BB473929 186.55 85.65 81.04 314.37 247.68 303.97 629.46 581.85 788.79 0.246493517 0.01887 0.00263775 /DB_XREF = gi: 16439785 /DB_XREF = BB473929 /CLONE = D330003M06 /FEA = EST /CNT = 5 /TID = Mm.214471.1 /TIER = ConsEnd /STK = 3 /UG = Mm.214471 /UG_TITLE = ESTs, Weakly similar to ENV1_HUMAN RETROVIRUS-RELATED ENV POLYPROTEIN (H. sapiens) 9574 solute carrier family 1 86.76 56.92 100.42 341.84 267.96 357.7 469.01 318.11 475.25 0.21893653 0.01905 4.04E−005 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1 8320 DEAD (Asp-Glu-Ala-Asp) box 112.56 127.64 180.35 447.67 410.04 494.24 453.03 489.33 871.51 0.265681561 0.01908 0.00016822 polypeptide 27 5137 nuclear respiratory factor 1 96.06 22.21 58.59 206.74 207.72 216.54 387.53 439.3 340.7 0.196671726 0.01923 0.00072954 12240 kelch-like 21 (Drosophila) 945.8 323.32 551.74 1286.9 1071.87 1407.3 2344.72 2073.51 1947.4 0.359439618 0.01923 0.00324608 1375 signaling intermediate in Toll 36.01 35.11 41.82 287.35 199.74 197.73 218.85 209.08 241.65 0.166774956 0.01935 7.77E−007 pathway-evolutionarily conserved 20342 kinesin family member 11 285.49 271.4 175.23 802.55 400.74 666.11 896.31 538.17 967.58 0.34279614 0.01938 0.00170065 32215 RIKEN cDNA 4833426J09 123.19 52.54 98.29 403.04 266.83 290.65 664.64 325.8 820.34 0.197755566 0.01942 0.00102827 gene 40316 (human) 76.89 53.93 138.9 311.28 272.58 273.85 386.44 406.16 550.1 0.245154312 0.01948 0.00031454 22448 ribosomal protein L37a 1002.33 507.96 700.13 1369.4 1086.69 1508.1 1821.16 2432.09 2770.43 0.402340412 0.01953 0.00609027 14883 similar to tripartite motif- 2079.61 1375.77 1494.31 3821.7 3156.2 3686.6 3576.25 3726.61 3888.5 0.452940224 0.01961 0.00012531 containing 43 17514 dolichol-phosphate (beta-D) 258.66 211.61 223.09 752.95 658.07 688.27 654.69 634.23 705.73 0.338725042 0.01961 4.11E−006 mannosyltransferase 1 20498 interleukin 17 receptor D 209.33 454.26 402.87 1218.7 961.8 1018.6 741.16 890.6 1180.07 0.354838495 0.01961 0.00052241 8691 YLP motif containing 1 212.15 172.37 259.8 629.55 420.34 439.07 700.52 1020 768.8 0.32391888 0.01969 0.00118415 1363 protein tyrosine phosphatase, 179.44 81.35 70.37 316.61 354.23 389.06 459.26 401.39 646.69 0.257989125 0.01974 0.00033685 non-receptor type 1 4707 RIKEN cDNA 2310008H09 197.94 200.34 46.69 511.26 431.89 592.74 490.78 359.97 815.86 0.277889149 0.01984 0.00233408 gene 29582 HECT domain containing 1 631.08 441.62 450.4 1198 860.21 1101.7 1757.53 1238.84 1402.21 0.403019138 0.01987 0.00082061 12090 pyridoxal (pyridoxine, vitamin 799 486.45 774.66 1353.4 1207.1 1465.8 1752.21 1584.83 2835.54 0.403985912 0.02 0.00279501 B6) kinase 19076 B-cell receptor-associated 467.79 406.25 272.93 836.98 845.26 926.32 1177.38 1170.25 1387.16 0.361629108 0.02 0.00035378 protein 31 22059 DNA segment, Chr 9, ERATO 78.25 101.45 110.24 395.68 368.76 211.62 565.85 296.89 522.68 0.24555787 0.02 0.00042704 Doi 720, expressed 14968 Casitas B-lineage lymphoma- 59.21 39.31 73.98 227.96 165.93 243.84 387.77 297.25 353.48 0.205819011 0.02013 0.00013549 like 1 3646 RIKEN cDNA 0610007P06 95.48 69.48 144.37 251.3 275.76 304.24 515.25 489.89 705.11 0.243418386 0.02016 0.00113655 gene 7606 caseinolytic peptidase X (E. coli) 305.08 204.23 250.93 827.98 642.13 720.65 860.05 674.03 951.76 0.325125091 0.02041 4.40E−005 14623 DNA segment, Chr 19, ERATO 1485.68 1003.23 618.92 2282.7 1674.85 1684 2958.22 2051.06 2943.84 0.457211329 0.02041 0.00546228 Doi 721, expressed 21740 ubiquitin specific peptidase 22 61.29 89.92 72.62 339.83 313.96 288.37 464.56 442.81 598.41 0.182872129 0.02041 3.09E−005 40844 RIKEN cDNA A530082C11 103.02 148.62 109.

459.34 222.66 476.49 456.67 365.07 541.49 0.28658217

0.02049 0.0004431 gene 41846 DNA segment, Chr 14, Abbott 1 186.91 203.53 137.66 493.13 316.45 653.17 637.61 639.35 503.72 0.325642915 0.02055 0.00045287 expressed 12366 Kruppel-like factor 9 16.35 11.35 21.12 152.11 133.07 165.7 191.43 117.35 292.03 0.092841046 0.02066 1.05E−005 16275 ankyrin repeat domain 10 957.77 535.96 734 1791.6 1402.79 1508.8 1900.92 1549.28 1875.29 0.444274929 0.02069 0.00043489 15513 solute carrier family 44, member 2 306.38 221.45 247.39 842.17 546.42 703.47 972.75 1046.06 1193.47 0.292296497 0.02083 0.00026173 30136 DEAD/H (Asp-Glu-Ala- 298.29 107.94 733.56 541.89 894.27 2088.9 557.59 1736.89 1228.52 0.323432306 0.02083 0.02150807 Asp/His) box polypeptide 31 5443 phosphatidylinositol glycan, 16.63 32.81 16.53 182.07 166.32 169.44 257.91 95.85 192.79 0.123959488 0.02098 3.41E−005 class N 11492 splicing factor, arginine/serine- 1024.33 1160.82 1136.04 2097 1886.86 1968.6 2810.75 2721.99 2515.66 0.474425893 0.02113 0.00046687 rich 15 /// similar to splicing factor, arginine/serine-rich 15 512 ribosomal protein L37a 554.13 423.04 428.11 1126.8 809.26 769.11 1242.39 1292.95 1650.52 0.407856568 0.02128 0.00194373 19536 TATA box binding protein 311.53 245.56 144.13 955.42 630.33 651.71 788.7 630.81 1019.52 0.299891585 0.02151 0.00027298 (TBP)-associated factor 13981 bolA-like 2 (E. coli) 1123.84 508.83 707.52 1607 1111.28 1182.5 2058.81 2007.06 2217.36 0.459584404 0.02174 0.00773939 16339 CNDP dipeptidase 2 29.26 96.28 61.29 542.76 229.08 165.59 150.97 419.23 414.14 0.194435338 0.02174 0.00246061 (metallopeptidase M20 family) 40577 RIKEN cDNA D330037H05 2109.33 1591.5 1770.31 3282.8 2998.53 3238.5 4490.22 4321.16 4046.76 0.488976197 0.02198 0.00074647 gene /// similar to La-related protein 4 (La ribonucleoprotein domain family member 4) /// similar to La-related protein 4 (La ribonucleoprotein domain family member 4) 23071 RIKEN cDNA 3300001M20 252.81 164.8 211.21 708.72 562.73 499.17 858.23 902.18 429.21 0.317566612 0.02222 0.0005967 gene 5178 RIKEN cDNA 1700021F05 1666.18 665.55 1064.07 2327.8 1899.07 2094.8 2300.95 2524.08 2681.17 0.491153722 0.02339 0.00283379 gene 9650 bone morphogenetic protein 216.85 211.07 155.24 631.62 531 550.21 566.68 440.17 655.89 0.345517942 0.02347 4.52E−005 receptor, type 1A 20927 ribosomal protein S15a 1300.6 959.53 1013.49 2281.4 1908 2020.4 1644.46 2363.4 2951.07 0.497181577 0.02358 0.00167999 9017 L-2-hydroxyglutarate 651.86 266.18 527.12 1034.2 590.33 965.17 1621.21 1345.63 1417.59 0.414435677 0.02367 0.00986099 dehydrogenase 19095 ribosomal protein S25 1492.69 819.24 1298.17 1951 1634.91 2069.3 2782.56 3268.32 3608.72 0.471453683 0.02381 0.00935608 23146 RIKEN cDNA 4933417E01 1387.41 981.03 1339 2342.5 1725.81 1965.4 2559.65 2606.75 2682.38 0.534117054 0.02392 0.00225043 gene 14122 ribosomal protein L37 /// similar 2088.46 1026.24 1539.86 2325.4 1980.64 2858.3 3213.87 3926.6 5118.59 0.47927296 0.02395 0.01585526 to ribosomal protein L37 1918 solute carrier family 12, member 2 967.39 592.93 609.84 1657.9 1103.01 1407.2 2393.42 1532.65 1828.34 0.437422461 0.0241 0.00251573 9201 proline, glutamic acid and 510.07 270.17 230.83 665.9 602.67 521.24 1107.52 1067.04 1083.99 0.400553843 0.02415 0.00573436 leucine rich protein 1 7982 RIKEN cDNA 2610012O22 269.15 194.81 225.6 623.68 421.41 548.5 719.07 776.11 829.08 0.352009393 0.02424 0.0003918 gene 6045 Son of sevenless homolog 1 324.06 248.6 173.51 684.56 368.73 779.87 937.33 493.55 698.66 0.376596765 0.02439 0.00317609 (Drosophila) 8238 RIKEN cDNA 2900073H19 238.99 108.15 83.52 574.46 220.64 424.2 345.06 612.16 561.13 0.314620203 0.02439 0.00372284 gene 1087 (formerly 2C), magnesium- 787.65 715.87 989.87 1836.5 1670.65 1777.8 1497.19 1797.05 1727.82 0.483825524 0.02463 0.00012463 dependent, gamma isoform 12224 solute carrier family 44, member 2 389.99 279.49 239.58 762.05 891.14 732.46 894.68 755.73 873.96 0.370287697 0.02469 5.28E−005 8376 poly (A) polymerase alpha 27.35 12.11 9.5 148.02 91.72 167.2 349.39 111.73 134.94 0.097627119 0.02475 0.00014113 15635 DEAD (Asp-Glu-Ala-Asp) box 1421.61 650.28 836.92 1354.5 1685.81 1727.6 2190.64 2797.01 3685.12 0.432837698 0.025 0.01163473 polypeptide 54 22224 WD repeat domain 81 30.24 51.94 30.12 149.76 94.94 145.32 314.53 347.69 678.34 0.129783079 0.025 0.00279921 6961 defensin related cryptdin 3 151.47 120.24 161.96 432.42 333.51 435.02 555.4 446.67 466.28 0.32493163 0.0251 4.13E−005 2811 metal response element binding 1221.23 1231.8 963.63 2148.1 1573.31 2029 2913.63 2368.89 2633.34 0.500013171 0.02513 0.00216856 transcription factor 2 38660 thioredoxin-like 2 /// similar to 256.9 121.83 146.19 592.86 461.89 532.76 354.26 505.22 432.44 0.364599938 0.02517 0.00046608 thioredoxin-like 2 19232 proteasome (prosome, 308.03 183.74 228.7 497.19 390.48 588.01 679.25 828.99 1020.79 0.359811322 0.02521 0.0025591 macropain) subunit, beta type 4 7130 GCN5 general control of amino 166.77 199.37 129.42 236.69 512.49 594.15 527.41 562.67 457.51 0.342838958 0.02525 0.00158602 acid synthesis-like 2 (yeast) 39148 protein phosphatase IA, 928.91 352.17 441.26 1276.6 1065.68 1257 1597.52 1131.12 1120.34 0.462479307 0.02525 0.0028015 magnesium dependent, alpha isoform 20760 RIKEN cDNA 6330412F12 1221.12 833.76 1060.24 2026.1 1856.48 2309.3 2009.25 2276.23 2705.78 0.472593299 0.02532 0.00036731 gene 30288 RIKEN cDNA D630023B12 231.8 124.88 215.74 650.6 584.87 451.15 354.09 367.11 666.9 0.372339595 0.02534 0.00162651 gene 6136 matrix metallopeptidase 19 680.52 322.99 248.89 1034.6 954 994.51 1010.69 1245.39 922.69 0.406499315 0.02538 0.00106165 504 glutamate dehydrogenase 1 522.62 453.19 388.25 953.35 635.51 724.4 1144.23 1119.64 1119.85 0.478871262 0.02542 0.00299594 19855 acyl-CoA synthetase long-chain 127.18 124.68 134.3 543.08 402.43 284.25 500.48 291.57 601.29 0.294430254 0.02548 0.000421 family member 4 10996 methionyl aminopeptidase 1 241.66 153.56 132.59 424.1 450.43 589.31 730.27 394.02 744.54 0.316749033 0.0255 0.00058301 12146 scaffold attachment factor B2 210.74 107.75 267.22 331.79 464.58 1217.3 391.5 663.29 603.9 0.31898202 0.0255 0.00753413 14456 eukaryotic translation initiation 608.3 392.9 580.62 1063.5 641.07 821.13 1540.18 1462.72 1376.89 0.458135605 0.02553 0.01083693 factor 4E member 2 24272 ribosomal protein S21 2211.44 1389.97 1767.7 3057.7 2659.66 3238.2 3772.83 3453.75 5642.06 0.492033374 0.02564 0.00500878 20122 histocompatibility 47 1061.18 593.13 563.78 1601.4 1273.75 1337.6 1610.56 1602.25 1546.14 0.494465907 0.02575 0.00117621 1829 integrin beta 5 20.55 31.81 35.62 138.64 106.21 113.56 245.56 233.83 262.94 0.159856097 0.02577 0.0001947 8820 peptidase (mitochondrial 103.32 47.96 17.42 213.06 180.94 210.53 289.87 282.06 241.71 0.237912239 0.02577 0.00089259 processing) alpha 8632 polymerase (RNA) II (DNA 546.89 407.89 194.5 750.55 562.77 678.85 1016.14 1159.35 1244.52 0.424701322 0.02586 0.00859166 directed) polypeptide H 18309 fibroblast growth factor 4 35.44 14.3 20.86 432.43 172.1 100.94 143.65 149.66 594.64 0.088614427 0.02591 0.00088338 29855 ankyrin repeat domain 35 194.21 126.07 115.62 458.93 307.25 358.15 396.59 1145.29 528.2 0.272914247 0.02595 0.00318398 23808 RIKEN cDNA 4632434I11 gene 448.86 431.73 363.62 671.77 596.73 936.9 1130.57 1078.94 1163.22 0.446102905 0.02597 0.0029039 16734 squamous cell carcinoma 321.84 208.57 257.48 621.17 329.5 867.92 525.03 704.23 1019.17 0.387453221 0.02604 0.00692468 antigen recognized by T-cells 1 20423 splicing factor, arginine/serine- 1714.9 1723.34 1637.59 2614.4 2538.82 2537.6 4326.68 3486.43 3541.53 0.533024807 0.02609 0.00359332 rich 15 /// similar to splicing factor, arginine/serine-rich 15 21533 ribosomal protein L41 2356.65 1636.04 2315.68 3506.7 3203.28 3590.5 4290.25 3926.82 4970.51 0.537155245 0.02618 0.00181749 11378 gb: AV003927 1053.61 887.11 842.46 1543.8 1584.51 1875.9 1827.18 1989.27 2602.7 0.487282112 0.0262 0.00095764 /DB_XREF = gi: 4780777 /DB_XREF = AV003927 /CLONE = 0610038F02 /FEA = mRNA /CNT = 8 /TID = Mm.89136.2 /TIER = Stack /STK = 8 /UG = Mm.89136 /LL = 15078 /UG_GENE = H3f3a /UG_TITLE = H3 histone, family 3A 10575 Yip1 domain family, member 4 1301.23 782.33 716.95 1652.4 1414.23 1672.3 2397.45 2218.58 2274.82 0.481613455 0.02632 0.00312624 27086 RIKEN cDNA 6720458F09 514.62 69.3 305.05 616.13 470.79 506.67 1261.3 1536.3 928.03 0.334248254 0.02643 0.01918525 gene 7894 WD repeat domain 36 254.38 272.47 200.29 610.23 547.12 595.16 573.36 653.39 981.04 0.367214605 0.0265 0.00024551 20279 UTP20, small subunit (SSU) 265.64 117.47 77.53 395.94 294.27 367.33 559.06 746.95 535 0.317841679 0.02655 0.0029134 processome component, homolog (yeast) 1828 integrin beta 5 24.85 44.95 37.18 101.84 100.6 157.78 300.13 259.71 279.75 0.178328235 0.0266 0.00087414 11029 F-box only protein 33 352.6 363.65 331.07 680.26 745.22 715.11 875.23 916.58 1126.49 0.414051304 0.0266 0.00023586 29619 BCL2-associated transcription 2093.59 1414.28 1845.33 3045.3 2613.48 2893.6 4169.09 3260.8 3703.5 0.543864934 0.02664 0.00241845 factor 1 7972 kinesin family member 22 361.65 356.42 276.4 873.55 734.19 599.86 722.03 806.28 1047.44 0.415804823 0.02667 0.00033015 20855 upstream binding transcription 926.95 606.37 732.79 1499.9 977.24 1296.7 1732.93 1838.77 1899.81 0.490214572 0.02667 0.00423551 factor, RNA polymerase I 3937 purine rich element binding 92.81 87.2 83.07 292.59 182.12 245.32 380.5 365.18 322.38 0.294258119 0.02669 0.00018866 protein B 15556 ataxin 10 17.33 32.34 12.45 228.41 198.1 179.58 181.72 19.95 77.06 0.140412739 0.02674 0.01259115 32318 Guanine nucleotide binding 38.16 26.14 37.97 167.8 192.62 140.2 315.19 211.09 159.05 0.172469328 0.02675 3.09E−005 protein (G protein), beta polypeptide 1-like 20865 transportin 3 498.71 536.39 322.85 1055.4 938.14 988.25 892.24 975.15 1289.64 0.442415456 0.02676 0.00038598 4981 sphingosine-1-phosphate 1139.7 516.96 256.51 1556.5 1386.43 1522.7 1138.21 1603.75 1205.39 0.454813871 0.02688 0.00679675 phosphatase 1 19730 gb: M11310.1 324.96 291.64 351.88 787.01 359.57 481.37 843.3 1266.51 1056.9 0.403982764 0.02688 0.01927971 /DB_XREF = gi: 192009 /FEA = FLmRNA /CNT = 3 /TID = Mm.1786.2 /TIER = FL /STK = 2 /UG = Mm.1786 /LL = 11821 /UG_GENE = Aprt /UG_TITLE = adenine phosphoribosyl transferase /DEF = Mouse adenine phosphoribosyltransferase (APRT), complete cds. /FL = gb: M11310.1 22636 glutamine fructose-6-phosphate 91.19 137.72 9.09 335.73 165.1 314.89 566.93 599.99 90.41 0.229613371 0.02691 0.02247234 transaminase 1 2926 ubiquitin-conjugating enzyme 294.34 174.38 235.24 787.87 546.3 553.52 647.84 590.18 714.62 0.366614327 0.02697 0.00012805 E2H 27358 RIKEN cDNA 9630055N22 51.52 68.1 41.88 364.66 211.27 222.89 271.25 214.45 185.62 0.219706967 0.02698 4.17E−005 gene /// similar to Feline leukemia virus subgroup C receptor-related protein 1 (Feline leukemia virus subgroup C receptor) (hFLVCR) 9307 sorting nexin 6 301.12 372.14 208.12 830.58 453.64 637.73 836.86 766.12 1038.77 0.386256765 0.02703 0.00175737 16924 torsin family 1, member B 614.56 254.05 272.1 1028.7 649.17 887.96 740.56 964.62 1195.38 0.417351759 0.02703 0.00265516 13406 RIKEN cDNA 1700081L11 279.8 322.06 289.78 766.08 332.23 382.41 846.57 836.8 863.11 0.442808899 0.02708 0.02078566 gene 4267 eukaryotic translation 631.46 328.73 441.06 971.21 1389.44 1088.4 1011.03 1046.31 2206.07 0.363373978 0.02717 0.0020725 termination factor 1 10910 nucleoporin 107 200.91 280.21 189.53 608.9 413.29 503.35 667.94 577.6 680.86 0.388564112 0.02717 0.00027743 3500 G patch domain containing 4 532.74 280.11 245.54 950.82 529.03 789.31 962.71 725.77 902.34 0.435553233 0.02727 0.00265492 16856 solute carrier family 12, member 2 171.34 87.64 209.04 527.45 337.21 487.48 447.9 572.27 515.56 0.324128164 0.02732 0.00041255 23353 GINS complex subunit 3 (Psf3 212.75 16.22 83.74 345.6 181.35 376.3 448.35 272.34 362.05 0.314915986 0.02737 0.00945197 homolog) 11567 thyroid hormone receptor 409.89 226.84 478.01 731.74 781.37 771.17 1116.95 1028.78 1020.12 0.409069141 0.0274 0.00102386 associated protein 3 20123 RIKEN cDNA D230025D16 566.99 244.72 230.85 773.96 545.87 752.66 969.51 843.84 1512.66 0.386240622 0.02747 0.00551593 gene 23022 gene model 608, (NCBI) 19.79 34.73 13.36 118.5 152.45 170.4 284.71 124.46 269.07 0.121258675 0.02747 8.52E−005 957 sarcosine dehydrogenase 102.85 51.26 39.67 276.87 330.62 409.42 265.49 87.25 247.39 0.239672488 0.02752 0.00405166 11737 integrin beta 4 binding protein 1478.64 784.12 1168.22 2140.2 1696.43 2027.5 2235.45 2368.91 2496.33 0.529274561 0.02756 0.00235946 12467 integrator complex subunit 7 15.64 11.95 9.45 107.56 81.04 69.17 167.85 135.22 200.6 0.097289347 0.02757 3.84E−005 28696 cDNA sequence BC031781 206.5 200.11 102.8 539.87 415.28 426.91 561.46 529.25 585.07 0.3331829 0.02762 0.0002035 2616 dodecenoyl-Coenzyme A delta 213.16 144.86 245.49 656.83 765.69 443.88 467.21 472 709.62 0.343368713 0.02765 0.00043803 isomerase (3,2 trans-enoyl- Coenyme A isomerase) 16782 Traf and Tnf receptor associated 86.91 90.66 92.25 320.57 262.64 310.65 271.8 329.04 442.44 0.278575632 0.02778 1.87E−005 protein 17246 piwi-like homolog 2 194.88 162.18 83.38 485.71 471.02 370.39 490.29 309.46 467.42 0.339545695 0.02778 0.00050921 (Drosophila) 28263 zinc finger protein 297B 346.22 252.82 249.98 689.62 506.85 491.93 824.26 739.66 843.71 0.414557511 0.02778 0.00089669 13852 CCR4-NOT transcription 624.54 555.94 435.99 1003.5 854.27 1131.5 1220.49 1252.71 1422.68 0.46955327 0.02788 0.00078009 complex, subunit 1 23277 biogenesis of lysosome-related 79.81 76.06 64.03 325.63 170.46 148.71 292.97 413.85 462.88 0.242380821 0.02793 0.00148942 organelles complex-1, subunit 2 42753 RIKEN cDNA 2010002M12 174.49 77.58 21.59 574.43 290.32 438.63 251.82 312.33 262.98 0.256896236 0.02799 0.00346194 gene 20191 cDNA sequence BC038286 125.97 73.92 68.54 284.36 290.06 209.54 343.44 337.31 491.7 0.274410783 0.028 0.00030981 39706 /DB_XREF = gi: 12854789 615.34 546.59 659.88 1182.5 1131.4 1245.5 1548.48 1390.42 1818.55 0.438098857 0.02804 0.00032472 /GEN = Hipk1 /FEA = mRNA /CNT = 3 /TID = Mm.160710.1 /TIER = ConsEnd /STK = 2 /UG = Mm.160710 /UG_TITLE = Mus musculus adult male testis cDNA, RIKEN full-length enriched library, clone: 4930557G23: homeodomain interacting protein kinase 1, full insert sequence /DEF = Mus musculus adult male testis cDNA, RIKEN full-length enriched library, clone: 4930557G23: homeodomain interacting protein kinase 1, 27310 G patch domain and KOW 61.52 159.03 86.57 532.82 393.07 275.19 336.31 260.97 331.72 0.288364756 0.02809 0.00056609 motifs 15631 Max dimerization protein 3 231.87 142.18 388.83 680.62 398.74 1726.9 635.95 544.19 1682.23 0.269158034 0.0282 0.01298519 1794 translocase of inner 445.43 218.47 297.38 1237.7 550.92 497.86 560.37 1173.81 1446.18 0.351674081 0.02825 0.01197186 mitochondrial membrane 10 homolog (yeast) 40394 RIKEN cDNA A230097K15 542.56 392.94 536.72 1135.4 943.8 714.8 1147.59 1095.12 1136.24 0.476993833 0.0283 0.00099635 gene 13932 cytochrome c oxidase, subunit 374.36 512.87 771.27 1560.4 816.01 1231.3 757.93 1492.77 1259.95 0.465978119 0.02834 0.00846149 XVII assembly protein homolog (yeast) 12583 nucleolar and coiled-body 1396.29 962.28 1269.5 2433.1 1712.66 2129 2601.27 2478.57 2899.66 0.509051699 0.02841 0.00166888 phosphoprotein 1 44733 RIKEN cDNA 2610510H03 1694.62 1302.55 1307.24 2154.8 2197.38 2580.1 2853.86 2696.93 3033.96 0.554799252 0.02841 0.00127502 gene 24057 RIKEN cDNA 6330548G22 1941.19 1205.89 1387.66 2922.2 2488.55 2691 2668.23 2814.66 3260.93 0.53838802 0.02846 0.00088299 gene 9979 G patch domain containing 4 1180.84 937.75 328.1 2341.4 1228.15 1953.3 2071.81 1558.28 1584.77 0.455720416 0.02857 0.00998652 15379 sorbitol dehydrogenase 27.38 63.24 77.06 217.25 225.56 241.16 303.1 194.63 333.28 0.221362658 0.02857 0.00015891 1395 CD320 antigen 376.3 186.45 150.95 519.75 347.27 458.89 885.75 732.05 898.14 0.371539753 0.02874 0.00681172 10147 homeodomain interacting 162.22 95.7 238.88 242.84 377.63 282.15 900.14 726.92 970.38 0.283880848 0.02874 0.01486244 protein kinase 1 /// similar to homeodomain-interacting protein kinase 1 40408 zinc finger and BTB domain 154.16 137.47 107.76 393.41 317.18 313.89 408.57 545.45 573.96 0.312945159 0.02885 0.00024451 containing 11 12344 La ribonucleoprotein domain 383.9 74.36 193.38 510.75 581.65 447.49 684.6 681.6 1010.2 0.332784344 0.0289 0.00428131 family, member 1 /// similar to la related protein isoform 1 801 proteasome (prosome, 317.41 182.75 245.98 577.9 392.79 559.5 873.25 678.68 1083.53 0.358234609 0.02896 0.00296154 macropain) subunit, alpha type 6 12365 gb: AW545056 575.81 256.8 387.06 829.02 524.34 892.94 1101.05 1108.62 1025.51 0.44501485 0.02907 0.00545304 /DB_XREF = gi: 7187569 /DB_XREF = C0190C04-3 /CLONE = C0190C04 /FEA = mRNA /CNT = 182 /TID = Mm.29909.1 /TIER = Stack /STK = 60 /UG = Mm.29909 /LL = 69023 /UG_GENE = 1810005K14Rik /UG_TITLE = RIKEN cDNA 1810005K14 gene 13580 RIKEN cDNA 9430010O03 252.11 205.75 110.44 548.01 407.24 529.86 651.64 535.7 411.67 0.368533001 0.0293 0.00067634 gene 29034 jumonji, AT rich interactive 37.2 22.61 18.65 222.58 113.9 160.57 93.92 144 233.42 0.162042152 0.02951 0.00011963 domain 1A (Rbp2 like) 8637 Bardet-Biedl syndrome 2 145.67 71.74 140.97 337.79 236.48 247.56 500.41 586.34 389.87 0.311844939 0.02961 0.00216673 homolog (human) 21932 Transcribed locus 449.07 163.81 87.36 583.75 309.89 572.13 653.87 636.22 766.49 0.397598194 0.0297 0.00950051 24471 TSC22 domain family 2 1111.19 838.9 701.35 1530.6 1318.86 1453.7 2101.28 2010.43 1899.33 0.514136405 0.0298 0.00250066 12713 transportin 3 236.77 170.07 152.07 455.61 333.47 459.35 782.62 552.05 536.83 0.358283679 0.0299 0.00088863 4235 zinc finger protein 644 25.19 29.71 183.22 387.55 173.75 307.41 242.2 191.55 329.75 0.291776181 0.03064 0.00413242 27956 RIKEN cDNA 4933439C20 214.02 187.62 218.88 489.82 385.39 354.78 580.99 667.79 1214.05 0.336068371 0.03073 0.00567336 gene /// phosphatidylserine decarboxylase 14945 proteasome (prosome, 673.17 339.26 437.73 823.99 814.83 842.51 1149.91 1450.18 1653.82 0.430618656 0.03081 0.00552425 macropain) subunit, alpha type 6 8311 CDNA clone IMAGE: 30031514 1455.82 885.16 844.81 1802.7 1683.15 1977.4 2026.15 1949.49 2208.37 0.547043051 0.03107 0.00167117 18423 stromal antigen 2 448.64 362.26 221.01 1147.6 777.91 1089.8 665.09 575.32 749.19 0.412363183 0.03116 0.00282021 7826 methionine adenosyltransferase 1253.06 613.26 919.4 1482.9 1371.95 1652.5 2216.98 1838.93 2120.48 0.521490234 0.03143 0.00499621 II, alpha 8396 zinc finger protein 639 651.33 592 510.89 1190.3 1159.1 1416.3 1011.3 1284.01 1188.3 0.483970154 0.03152 0.00017759 19114 WD repeat domain 36 205.63 144.93 118.6 423.92 347.67 404.86 409.04 556.77 672.92 0.333307284 0.03161 0.00038691 919 ubiquitin A-52 residue 1179.37 800.7 703.02 1290.2 1670.19 1344.1 2225.44 1773.66 3566.28 0.452084904 0.0317 0.01417489 ribosomal protein fusion product 1 /// similar to ubiquitin A-52 residue ribosomal protein fusion product 1 /// similar to ubiquitin A-52 residue ribosomal protein fusion product 1 /// similar to ubiquitin A-52 residue ribosomal protein fusion product 1 6104 brix domain containing 1 189.12 152.83 356.96 579.34 457.58 505.53 797.43 691.14 566.73 0.388526162 0.03179 0.00117216 14528 gene model 288, (NCBI) 611.12 289.52 223.86 897.94 493.54 694.95 841.18 913.47 964.44 0.468003463 0.03188 0.00748606 14234 ribosomal protein S3 1603.17 992.86 1195.88 2140 1511 1797.1 2583.61 2433.02 3136.49 0.557583805 0.03191 0.01375262 1610 GRIP1 associated protein 1 156.21 52.05 43.1 267.72 230.72 274.17 284.24 349.37 343.89 0.287250516 0.03198 0.00064653 607 arginyl-tRNA synthetase 475.28 273.88 474.37 856.71 656.69 777.19 931.87 958.54 1034 0.469234899 0.032 0.00130575 8157 general transcription factor IIIC, 212.08 99.85 122.9 316.44 273.49 369.01 425.12 499.92 698.25 0.336786421 0.03209 0.00211539 polypeptide 5 10540 peroxisome proliferative 902.33 445.31 392.62 1139.4 999.53 1033.5 1236.07 1335.21 2000.98 0.449403209 0.03215 0.00487984 activated receptor, gamma, coactivator-related 1 17591 zinc finger protein 292 33.35 44.66 45.16 200.8 146.72 175.4 256.79 209.89 116.94 0.222621866 0.03216 6.65E−005 16780 histocompatibility 47 1837.26 1122.62 1324.02 2610 1889.17 2344.4 2583.68 2481.42 2674.07 0.587533816 0.03217 0.00342811 257 eukaryotic translation initiation 627.16 426.41 780.66 1198.3 1019.38 1204.3 1897.89 1173.9 2308.62 0.41675632 0.03226 0.00484988 factor 3, subunit 3 (gamma) 13101 heterogeneous nuclear 1618.69 1405.47 1477.8 2463.2 2093.97 2498.9 2936.45 2830.56 2597.97 0.583869773 0.03233 0.00099967 ribonucleoprotein A/B 33525 Transcribed locus 83.97 35.52 295.51 432.87 220.51 436.57 389.83 242.22 680.37 0.34549216 0.03235 0.01240034 2568 ribosomal protein L30 /// similar 1254.95 735.95 965.54 1689.5 1596.35 1943.3 1668.9 1938.22 2788.5 0.508643152 0.03235 0.00325586 to ribosomal protein L30 /// similar to ribosomal protein L30 /// similar to ribosomal protein L30 /// similar to ribosomal protein L30 7517 RIKEN cDNA 1810009K13 143.62 57.05 68.62 322.65 136.04 252.87 427.73 276.99 553.43 0.273431114 0.03236 0.00435699 gene 19614 TIP41, TOR signalling pathway 1754.37 1366.54 1274.92 2383.4 2108.26 2070.9 2846.61 2746.03 2667.1 0.593140169 0.03241 0.0026507 regulator-like (S. cerevisiae) 5982 protein phosphatase 2 (formerly 551.48 339.48 280.15 775 546.79 692.17 928.41 1201.26 1257.08 0.433687423 0.03243 0.00657847 2A), catalytic subunit, beta isoform 9877 influenza virus NS1A binding 975.18 492.65 387.23 858.37 991.15 1163.2 1663.53 2058.91 1252.97 0.464454715 0.03248 0.01279151 protein 16885 chromosome segregation 1-like 121.07 97.77 145.66 350.27 345.42 378.07 298.67 387.07 410.09 0.336008186 0.03254 2.39E−005 (S. cerevisiae) 29192 cleavage and polyadenylation 17.6 44.66 34.12 174.3 133 221.06 127.6 192.74 129.81 0.196993388 0.03256 8.84E−005 specific factor 6 8733 transmembrane emp24 protein 207.72 120.4 223.01 611.94 436.79 466.68 476.75 506.84 551.44 0.361344593 0.03257 0.00015655 transport domain containing 5 8642

180.91 186.12 138.75 443.86 379.97 493.4 573.62 451.43 424.69 0.365584014 0.03261 5.25E−005 /DB_XREF = gi: 14318706 /FEA = FLmRNA /CNT = 134 /TID = Mm.29500.1 /TIER = FL + Stack /STK = 29 /UG = Mm.29500 /DEF = Mus musculus, hypothetical protein FLJ10788, clone MGC: 6884 IMAGE: 2651599, mRNA, complete cds. 27736 RIKEN cDNA C730049O14 468.55 201.7 280.69 854.88 650.64 580.29 733.69 724.56 697.53 0.448388458 0.03263 0.00126179 gene 15165 glutaredoxin 2 (thioltransferase) 187.31 23.63 26.17 284.27 207.99 195.31 286.09 281.75 295.36 0.305796475 0.03264 0.00335924 34773 coiled-coil domain containing 327.65 244.56 99.43 681.69 370.27 538.09 732.89 447.88 631.69 0.394790904 0.03268 0.00477611 66 22170 hexosaminidase B 466.76 254.86 157.95 680.55 374.26 443.5 767.08 800.87 731.5 0.463204626 0.03271 0.01339699 41702 PREDICTED: Mus musculus 52.96 7.24 13.47 124.13 107.95 76.94 201.8 231.95 168.21 0.161737909 0.03274 0.00107041 similar to aspartoacylase-3 (LOC629627), mRNA 8599 mitochondrial ribosomal protein 84.99 90.76 80.52 172.16 157.7 188.73 395.52 436.4 635.42 0.258085632 0.03279 0.00751919 S6 12768 zinc finger protein 644 15.61 32.03 46.1 366.23 40.06 93.41 192.4 133.37 321.07 0.163518063 0.03279 0.01131652 19905 junction-mediating and 169.13 233.3 148.29 543.3 293 427.21 657.56 428.21 656.69 0.366417496 0.03284 0.00158297 regulatory protein 13983 bolA-like 2 (E. coli) 640.93 283.51 474.89 891.08 567.86 705.83 1189.82 1104.23 1324 0.483961112 0.03286 0.01507785 12572 BCL2-associated transcription 2243.95 1513.18 2041.07 3292.2 2693.98 3229.5 3913.71 3100.47 3629.4 0.583930579 0.03293 0.00247576 factor 1 13491 phosphatidylinositol 4-kinase 106.26 77.85 116.88 271.2 295.15 204.29 626.53 277.93 551.44 0.270365679 0.03294 0.00205473 type 2 alpha 8482 nucleolar complex associated 2 984.9 484.36 571.5 1289.3 1202.67 1169.9 1470.81 1389.35 1671.63 0.498135738 0.03297 0.00193977 homolog (S. cerevisiae) 18925 hippocampus abundant gene 1626.37 984.96 926.25 1800.2 1384 1711.6 2541.97 2468.73 3077.91 0.544894435 0.03302 0.02020823 transcript 1 29821 general transcription factor III C1 649.54 697.58 431.58 1080.6 901.53 1212.7 1451.96 1192.11 1707.24 0.471422324 0.03303 0.00235796 28901 RIKEN cDNA 4932408B21 57.42 28.78 34.91 186.88 112.52 187.44 217.22 178.97 178.07 0.228272547 0.03307 6.72E−005 gene 27240 nucleoporin 98 708.33 558.18 484.95 1086:1 858.65 840.28 1314.93 1255.99 1590.24 0.504291543 0.0331 0.00479921 16347 DEAD (Asp-Glu-Ala-Asp) box 691.31 341.98 479.23 933.21 720.44 1161.8 1068.9 1079.18 1463.87 0.470644611 0.03313 0.00388951 polypeptide 21 12433 general transcription factor IIIC, 134.75 114 117.11 326.86 320.97 220.76 337.18 352.3 512.23 0.3534367 0.03314 0.00046942 polypeptide 2, beta 16878 nuclear fragile X mental 735.99 520.27 616.98 1152 1106.58 1108.4 1669.92 1264.41 1709.52 0.467676882 0.03316 0.00109882 retardation protein interacting protein 1 20819 ubiquitin-conjugating enzyme 1431.97 1109.57 1108.32 1340.1 1457.9 1689.9 3079.28 3096.31 3132.89 0.529102477 0.03318 0.04620446 E2C 15367 adhesion regulating molecule 1 2376.07 1243.06 1825.49 2794.9 2622.99 3207.4 2488.6 3090.31 3801.22 0.604778024 0.0332 0.00947177 35487 TatD DNase domain containing 1 49.58 54.22 10.94 234.77 114.06 144.99 202.21 154.66 288.54 0.201434302 0.03323 0.00129083 26869 guanine monphosphate 122.92 142.78 107.6 432.72 251.71 382.77 333.62 321.76 588.17 0.323098561 0.03324 0.0004596 synthetase 17750 Zinc finger protein 644 18.41 38 141.75 287.13 126.78 223.87 231.07 167.08 286.89 0.299602365 0.03327 0.00457717 10563 ring finger protein 11 81.84 78.97 111.45 413.57 203.45 266.73 291.63 298.49 401.2 0.290399825 0.03333 0.00019063 22525 ribosomal protein L23 1694.63 1408.99 1322.27 2543.8 2122.05 2440.6 2267.39 2629.52 3731.63 0.562553901 0.0333 0.00413512 41190 methyltransferase like 2 201.66 120.68 113.21 444.44 370.04 370.14 371.11 445.47 374.11 0.366731079 0.0333 9.87E−005 22167 CNDP dipeptidase 2 22.88 61.95 32.07 330.23 79.86 180.33 84.76 218.18 158.8 0.22220955 0.0334 0.00380262 (metallopeptidase M20 family) 1037 craniofacial development 632.43 487.38 759.93 1272.7 874.72 1051.5 1332.88 1198.09 1629.04 0.510874572 0.03341 0.00315993 protein 1 19490 Rho GTPase activating protein 8 561.58 232.84 159.57 755.26 534.11 863.06 783.69 493.49 842.26 0.446638123 0.03343 0.00744318 23936 RIKEN cDNA 2810004A10 611.4 319.12 196.57 795.57 922.98 799.63 775.73 795.6 585.57 0.482169289 0.03346 0.00506537 gene 38670 fibroblast growth factor receptor- 170.84 122.93 50.89 527.58 138.93 388.29 327.68 457.46 183.49 0.340669062 0.03349 0.01815324 like 1 13982 bolA-like 2 (E. coli) 667.26 327.26 632.69 997.91 533.2 734.58 1519.41 1322.18 1597.39 0.485396 0.03353 0.03999237 21923 gene /// RIKEN cDNA 936.03 563.58 807.33 1249.3 1254.37 1612.3 1349.57 1971.41 2092.11 0.48419199 0.03354 0.00309151 5830484A20 gene /// similar to Sp110 nuclear body protein /// 7522 sortilin 1 47.52 42.59 83.69 467.9 79.92 299.98 346.19 142.97 127.38 0.237376566 0.0336 0.01339749 20481 SDA1 domain containing 1 1362.71 859.8 1118.87 2204.8 1724.2 2050.9 2051.86 2375.74 1968.44 0.539978684 0.03364 0.00101078 677 cathepsin C 620.48 261.03 388.32 1142.3 623.95 597.3 1072.15 767.24 1113.22 0.47772632 0.03365 0.01077421 12728 polymerase (RNA) III (DNA 1173.78 856.85 818.59 1893.6 1486.88 1477.6 1672.05 1702.36 2013.3 0.556175975 0.03366 0.00133563 directed) polypeptide E 171 ribosomal protein S26 1005.17 525.6 798.19 1159.7 1132.3 1291 1650.32 1768.46 3066.94 0.462613383 0.03373 0.01726663 21453 ribosomal protein S8 2653.11 1674.67 2415.56 3453.2 3323.49 3368.9 3676.28 3927.51 5180.08 0.588181318 0.03373 0.00586965 18058 AF4/FMR2 family, member 4 66.6 79.82 102.25 260.49 269.44 166.59 260.12 196.38 405.8 0.319049024 0.0338 0.00066396 2114 torsin family 1, member B 611.51 202.39 243.41 852.18 486.97 714.88 856.26 824.23 655.93 0.481640834 0.03386 0.00820538 7324 metastasis-associated gene 808.65 595.65 569.46 1393.2 875.73 1334.4 1064.04 1538.48 1479.47 0.513642858 0.03395 0.00325528 family, member 2 20207 PHD finger protein 17 45.11 97.31 48.99 150.19 219.06 156.4 230.13 395.67 311.67 0.261646345 0.03398 0.00115284 22719 myelin protein zero-like 1 26.63 58.06 86.57 211.23 241.63 192.89 146.38 553.53 185.92 0.22363833 0.034 0.00221299 13129 mediator of RNA polymerase II 88.18 61.52 35.11 199.79 152.12 177.8 282.24 471.76 209.96 0.247457604 0.03405 0.00141734 transcription, subunit 8 homolog (yeast) 33684 activating transcription factor 7 465.25 439.02 701.39 1507.1 999.44 1317.4 817.23 803.3 1090.48 0.491410733 0.03407 0.00480905 interacting protein 2 9652 bone morphogenetic protein 30.66 33.23 24.13 164.86 83.03 98.67 231.61 148.75 169.39 0.196405262 0.03412 0.00020267 receptor, type 1A 20214 RNA binding motif protein 5 571.27 767.82 724.89 970.89 1114.44 1258.3 1664.76 1551.93 1412.32 0.517765759 0.03415 0.00244522 16715 spermatogenesis associated 5 137.92 102.31 61.45 459.08 274.64 228.49 327.14 221.78 356.12 0.323127594 0.03417 0.00093717 24191 cancer susceptibility candidate 5 152.1 164.87 125.69 368.06 261.62 337.15 517.57 426.13 722.68 0.336213215 0.03421 0.00163987 /// similar to cancer susceptibility candidate 5 isoform 2 27633 vitamin K epoxide reductase 158.7 49.79 76.93 398.67 216.04 284.84 293.31 284.28 381.74 0.307088139 0.03423 0.00085041 complex, subunit 1-like 1 7003 WD repeat domain 77 1094.94 580.22 464.08 1369.7 1345.02 1526.4 1197.88 1576.35 1489.59 0.503058814 0.03427 0.00254454 344 glycine decarboxylase 449.54 174.14 151.67 613.06 279.64 804.84 631.24 715.88 615.34 0.423688525 0.03431 0.01299645 1917 solute carrier family 12, member 2 500.3 207.9 501 1012.6 574.08 711.55 831.2 898.12 1082.66 0.473252358 0.03432 0.00723914 15722 DEAD (Asp-Glu-Ala-Asp) box 385.08 297.48 284.8 475.57 561.19 524.9 865.28 1016.7 851.49 0.450445039 0.03434 0.00548161 polypeptide 17 3811 DNA segment, human 157.43 142.21 194.44 493.98 482.27 475.73 458.09 304.57 395.93 0.378522698 0.03438 0.00016711 DXS9928E 14157 RIKEN cDNA 2610101J03 1078.89 693.47 683.97 1413 1116.89 1409.9 2146.69 1725.33 1648.32 0.519305374 0.0344 0.00470655 gene 21888 death inducer-obliterator 1 489.88 352.87 242.07 885.74 746.18 817.23 629.22 636.1 1048.16 0.455555019 0.0344 0.00196002 6127 Willi/Angelman syndrome 2 146.49 115.62 62.97 277.82 180.98 205.37 423.86 504.78 426.8 0.32192354 0.03448 0.00497845 homolog (human) 10418 pantothenate kinase 3 571.77 464.21 419.81 1151.2 770.81 1060.5 873.11 919.21 1010 0.503316456 0.03455 0.00060585 7942 torsin family 2, member A 56.41 57.84 15.89 182.4 117.93 153.01 167.89 264.45 201.53 0.239401772 0.03455 0.00088711 6639 sorting nexin 3 120.78 103.65 110.21 326.23 216.07 202.87 341.2 336.98 604.44 0.330053901 0.03456 0.00250308 3398 abhydrolase domain containing 6 330.84 210.9 246.57 422.75 380.61 691.33 684.84 889.36 650.71 0.423868158 0.03459 0.00458787 640 translocase of inner 878.17 670.48 908.3 1804.6 1319.02 1419.3 1722.45 1433.31 1537.61 0.532026734 0.03462 0.00067228 mitochondrial membrane 8 homolog a1 (yeast) 7006 protein kinase C, delta 411.25 383.64 115.26 712.82 315.54 733.67 910.26 661.36 733.23 0.447591274 0.03465 0.02184294 15510 Williams-Beuren syndrome 387.38 65.5 224.42 655.34 402.2 299.57 683.74 452.6 930.59 0.395614537 0.03469 0.0206498 chromosome region 1 homolog 1970 midasin homolog (yeast) 72.03 19.88 33.69 203.55 127.77 190.18 139.01 179.55 201.68 0.241135024 0.03474 0.0003368 3936 purine rich element binding 1414.47 939.03 992.32 1815.5 1442.75 1699.3 2127.53 2327.95 2198.24 0.576307096 0.03476 0.00541495 protein B 11214 thioesterase superfamily member 4 209.2 140.63 221.22 557.73 459.97 598.38 413.32 339.06 663.38 0.376701937 0.03481 0.00078993 20608 RIKEN cDNA 2610304G08 85.77 64.41 24.73 216 142.41 211.13 393.72 237.84 189.99 0.251471867 0.03483 0.00126552 gene 401 KTI12 homolog, chromatin 204.06 74 121.41 306.83 197.69 220.06 546.92 436.97 511.52 0.359884504 0.03484 0.00978944 associated (S. cerevisiae) 4187 gb: AV006589 750.81 258.88 477.14 770.5 790.87 855.25 1131.06 1138.45 1223.11 0.503222073 0.03488 0.00891259 /DB_XREF = gi: 4783576 /DB_XREF = AV006589 /CLONE = 1100006A23 /FEA = EST /CNT = 1 /TID = Mm.198379.1 /TIER = ConsEnd /STK = 0 /UG = Mm.198379 /LL = 99251 /UG_GENE = AV006589 /UG_TITLE = expressed sequence AV006589 20263 ATP-binding cassette, sub- 1974.08 1512.28 1591.36 2799.7 2379.24 2881.9 3476.53 3087.76 3006.5 0.575978511 0.03492 0.00134869 family F (GCN20), member 1 6063 nuclear receptor coactivator 6 96.49 66.05 71.48 230.69 170.41 262.11 380.42 250.08 337.13 0.286993206 0.035 0.00026083 interacting protein 7582 associated 3 772.56 580.96 729.21 1398.6 1166.76 1297.1 1691.5 1392.13 1417.23 0.498064757 0.03503 0.00033862 7829 signal recognition particle 1178.28 396.35 506.11 1274.3 1169.1 1329.2 1193.62 1444.27 1684.77 0.51406442 0.03505 0.00684649 receptor (‘docking protein’) 1149 solute carrier family 34 (sodium 1671.27 1451.17 1598.15 2771.9 2571.18 2756.1 2423.89 2605.98 2900.33 0.588995153 0.03509 0.00034828 phosphate), member 2 23975 RIKEN cDNA D530033C11 15.02 9.78 12.59 135.75 30.07 112.3 106.24 70.57 148.16 0.12399476 0.03512 0.00060996 gene 3060 T-cell immunoglobulin and 695.08 248.62 328 826.75 592.21 729.65 1034.03 1032.95 1807.45 0.422278451 0.03518 0.01412352 mucin domain containing 2 7965 integrator complex subunit 4 108.79 143.67 117.13 263.16 266.45 284.38 553.99 382.53 444.37 0.336774676 0.0352 0.00079899 15134 ribosomal protein S8 2879.67 1822.12 2555.47 3715 3487.55 3736.8 3939.03 4199.88 5464.29 0.591403484 0.03525 0.0054164 10616 sarcolemma associated protein 302.65 177.5 294.36 828.0

459.32 599.96 670.2 546.64 765.82 0.400268737 0.03526 0.00086754 19022 folate receptor 1 (adult) 295.13 157.89 124.56 512.13 492.87 451.56 490.43 421.28 529.28 0.39866784 0.03526 0.00048712 39934 RIKEN cDNA 2410019A14 948.04 617.96 722.82 1276.2 1461.42 1309.

1701.46 1341.04 1647.3 0.523969663 0.03527 0.00085077 gene 27541 hypothetical protein 29.79 29.13 17.85 111.26 148.96 160.01 179.04 101.84 124.88 0.185886028 0.03534 1.86E−005 5430421B17 13353 cyclin L2 366.32 286.12 242.58 661.8 568.59 569.17 785.19 691.43 896.88 0.428951417 0.03535 0.00044813 8628 cleavage and polyadenylation 437.6 464.66 259.65 801.65 552.59 757.67 924.15 849.4 912.93 0.484291606 0.03542 0.00233476 specific factor 4 15335 RIKEN cDNA 2810409H07 74.5 32.14 51.2 212.66 134.11 162.73 340.99 117.8 348.25 0.239780029 0.03544 0.00207122 gene 21143 RIKEN cDNA 2900097C17 55.86 42.84 49.42 191.63 97.34 143.81 238.34 247.68 216.44 0.260949227 0.03544 0.00048204 gene 27810 mannosidase 2, alpha 2 187.42 198.71 152.25 448.07 341.04 401.19 578.87 431.83 634.48 0.379745228 0.03549 0.00040675 21839 B-cell receptor-associated 682.51 376.13 741.32 1355.9 913.47 1360.2 1021.68 1106.77 1232.25 0.514990859 0.03564 0.00340949 protein 31 27178 spermatogenesis associated 2 1161.91 964.7 1257.96 2142.9 1761.61 1953.7 1664.48 2350.84 2119.38 0.564429895 0.03571 0.00117285 27596 Expressed sequence AI195381 164.06 50.24 97.33 314.61 235.05 369.8 208.02 349.59 306.67 0.34941191 0.03579 0.00171003 8359 SEH1-like (S. cerevisiae 34.37 35.38 21.55 153.44 52.09 164.71 185.96 151.36 190.7 0.203281901 0.03581 0.0010864 21158 phosphoserine aminotransferase 1 762.08 527.82 423.16 1268.1 1111.16 1110.2 1163.28 1112.98 1052.34 0.502508789 0.03586 0.00058213 20989 ribosomal protein L37 265.68 159.08 539.01 502.7 517.5 685.71 1247.62 1948.95 3246.7 0.236531774 0.0359 0.02475044 20676 reticulon 4 1574.4 894.92 1056.14 1903.9 1775.22 1903.2 2525.25 2161.78 2275.69 0.562051115 0.03594 0.0030746 11523 ornithine decarboxylase, 1456.62 734.62 1199.01 1588.9 1504 1639.4 2484.21 2389.48 2308.26 0.569109376 0.03598 0.01491284 structural 1 /// similar to Ornithine decarboxylase (ODC) 6500 lysophospholipase 3 47.88 151.19 39.47 198.56 143.95 151.5 374.75 347.89 480.81 0.281055224 0.03599 0.00760032 7881 transmembrane protein 49 214.62 75.2 94.84 335.84 369.33 256.77 372.8

272.48 580.32 0.351681104 0.03602 0.00252792 10737 SNAP-associated protein 273.69 269.17 162.25 547.62 550.93 515.68 525.29 571.28 535.32 0.434432492 0.03605 0.00015943 9707 leukocyte specific transcript 1 150.44 125.82 60.94 231.93 196.75 216.83 442.18 529.47 633.7

0.29961748 0.03608 0.00854339 10862 cyclin G associated kinase 189.88 169.84 165.37 414.6 338.87 451.82 691.18 343.8 583.16 0.371951846 0.03617 0.00088473 12376 p53 and DNA damage regulated 1 548.67 181.79 376.6 789.75 643.57 739.9

846.2

866 924.2 0.460350463 0.03618 0.00344332 12925 enhancer of rudimentary 971.59 772.44 792.75 1277.8 1052.43 1432.2 1720.87 1915.14 1795 0.551868619 0.03625 0.0060476 homolog (Drosophila) 980 fibrillarin 684.3

450.34 486.4 856.32 653.88 1067.7 1220.0

1189.37 1652.28 0.488299694 0.03627 0.01051729 29430 trans-acting transcription factor 6 683.7

635.

523.7 922.49 833 1035.4 1440.35 1366.46 1588.41 0.512799033 0.03632 0.0059473 22752 phosphoglucomutase 3 117.47 70.55 76.49 280.19 226.01 244.57 283.4

365.0

342.8 0.303680189 0.03636 8.87E−005 14032 seizure related 6 homolog like 2 23.56 3.91 6.09 51.61 168.7 132.62 164.68 29.4 81.1 0.106860263 0.0364 0.0018215 21869 similar to ubiquitin A-52 residue 1092.71 549.03 901.08 1326.5 1044.1 1421.4 1855.2 1998.4 2994.86 0.477956614 0.03646 0.02013608 ribosomal protein fusion product 1 15947 expressed sequence AI593864 59.53 130.96 145.41 238.39 245.29 390.12 422.46 217.98 589.3 0.319366401 0.03648 0.00409729 360 ankyrin repeat domain 10 1631.2 1255.22 1597.8 2366.3 1976.89 2233.4 2873.13 2724.96 2719.92 0.602127754 0.03656 0.00313083 13232 brix domain containing 5 249.7 149.34 101.69 500.78 396.36 411.4 449.86 312.53 480.19 0.392556995 0.03664 0.00094472 7575 SWI/SNF related, matrix 169.06 151.5 175.74 345.56 264.16 208.33 557.93 543.22 522.86 0.40646012 0.03665 0.01048791 associated, actin dependent regulator of chromatin, subfamily c, member 1 847 developmental pluripotency 637.03 556.11 625.16 1200.8 846.84 1332.8 1135.98 1117.74 2353.11 0.455300635 0.03672 0.00785991 associated 5 19522 WW domain containing adaptor 1020.92 699.47 883.58 1264.2 1408.61 1531 1740.17 1592.41 1789.74 0.558426352 0.03672 0.0014871 with coiled-coil 21628 uridine monophosphate 98.18 94.72 68.1 288.06 248.98 175.65 306.21 226.92 452.59 0.307346283 0.0368 0.00065722 synthetase 15391 ras responsive element binding 141.53 165.74 217.71 421.99 422.79 503.87 510.83 456.58 227.76 0.41274933 0.03686 0.00261093 protein 1 13913 Heterogeneous nuclear 22.26 32.92 25.16 157.59 122.26 145.62 79.73 130.3 273.63 0.1767404 0.03688 0.00020361 ribonucleoprotein U 28627 solute carrier family 19 485.43 151.49 233.17 737.26 511.1 592.5 613.8 620.42 958.53 0.431419994 0.03694 0.00454474 (sodium/hydrogen exchanger), member 3 18771 elongation factor RNA 604.78 436.5 353.74 1119.5 733.54 995.87 939.53 968.34 900.94 0.493137707 0.03696 0.00098 polymerase II 2 10803 TBC1 domain family, member 126.56 81.16 223.11 336.16 248.27 209.16 442.89 430.88 702.71 0.363558882 0.037 0.01061646 20 13848 expressed sequence AA408556 215.08 107.35 165.18 295.85 310.39 421.99 454.92 383.23 796.93 0.366168414 0.03707 0.00397733 1685 XPA binding protein 1 410.06 452.6 766.7

1401.7 1053.22 878.62 1090.91 995.33 1162.3

0.495088976 0.03712 0.00193188 19044 ERGIC and golgi 3 44.81 65.7 48.44 93.9 72.33 245.35 177.49 438.27 277.99 0.243539948 0.03714 0.01416792 27096 like) 10 20.8 3.27 12.57 89.8 103.08 86.03 136.13 47.95 210.38 0.108825757 0.03717 0.00063987 727 6-phosphofructo-2- 63.36 20.84 112.36 213.6 178.27 137.99 367.86 210.92 349.81 0.269546436 0.03724 0.00380938 kinase/fructose-2,6- biphosphatase 3 2739 RGS16 351.74 117.12 76.23 503.15 162.89 413.91 695.01 773.54 1692.2 0.257075483 0.03727 0.02968997 24940 DNA segment, Chr 8, Brigham 118.78 53.72 55.79 186.53 261.76 155.04 261.02 198.73 393.02 0.313563629 0.0373 0.00157746 & Women's Genetics 1414 expressed 10152 heat shock protein 110 1398.12 830.88 1073.63 1668.8 1565.54 2160 2008.28 1789.22 316.3 0.573965664 0.03731 0.004098 19155 kinesin family member 22 398.22 450.27 354.46 841.6 654.4 559 989.59 886.55 947.43 0.49314973 0.03736 0.00219119 7723 phosphoribosylaminoimidazole 391.13 442.83 339.16 827.89 516.64 792.43 952.32 677.57 929.92 0.499543303 0.03737 0.002641 carboxylase, phosphoribosylaminoribosylami 11302 jumonji, AT rich interactive 1673.42 942.45 1166.08 2053.4 1794.29 2099.4 2527.42 2125.87 2560.26 0.574734303 0.03738 0.00388238 domain 1B (Rbp2 like) 13496 ribosomal protein L38 1996.91 1375.66 2224.12 2929.6 2359.26 2980.6 2797.37 3517.85 4415.85 0.58910883 0.03741 0.01204374 18935 eukaryotic translation initiation 2312.87 1828.13 2131.71 3207.1 2800.93 3286.2 3402.34 3230.56 3391.04 0.649411718 0.03742 0.00176804 factor 4E /// hypothetical LOC630527 10415 translocase of inner 1200.54 871.03 958.28 1480.2 1104.86 1390.9 2541.11 2448.39 2310.83 0.537385623 0.03744 0.02830428 mitochondrial membrane 17a 11848 TNFAIP3 interacting protein 1 321.33 225.29 228.01 806.72 511.77 512.88 594.28 486.89 1024.8 0.393478846 0.03745 0.00199172 29413 DCN1, defective in cullin 208.2 181.55 129.44 483.09 350.59 483.79 304.94 421.64 437.94 0.418365908 0.0375 0.0005084 neddylation 1, domain containing 3 (S. cerevisiae) 19069 myc induced nuclear antigen 198.52 93.12 89.6 515.36 223.46 260.41 415.61 176.74 570.73 0.352622889 0.03754 0.01215379 22250 karyopherin (importin) alpha 1 487.51 288.58 322.38 647.95 625.2 643.16 953.35 982.64 857.55 0.466456469 0.03755 0.00191203 20912 ribosomal protein S24 1503.87 981.91 1382.51 1903.5 1484.96 1825.7 2662.36 2502.71 2852.52 0.584700379 0.03757 0.01797688 40811 gem (nuclear organelle) 66.66 15.96 108.86 341.52 213.42 149.85 199.83 127.31 288.52 0.290022341 0.0376 0.00628726 associated protein 5 19408 RIKEN cDNA 1810020D17 70.67 116.83 133.45 300.46 275.02 220.85 330.43 391.71 361.99 0.341352648 0.03761 0.00033814 gene 16317 GM2 ganglioside activator 1460.32 965.39 1158.55 1585.9 1681.36 1877.4 2813.6 2472.1 2183.15 0.568322595 0.03761 0.00878651 protein 15388 RIKEN cDNA 2610042O14 385.77 161.98 351.7 704.56 394.83 574.8 563.17 1018.26 1190.97 0.4045572 0.03763 0.01369527 gene 18450 brix domain containing 1 368.46 490.29 890 1496.2 1126.8 1048.1 945.53 776.39 1481.18 0.508783516 0.03764 0.01101669 72 oncogene family 79.2 22.75 80.1 172.14 152.77 222.72 326.45 170.57 344.7 0.262064994 0.03765 0.00211936 22384 DEAD (Asp-Glu-Ala-Asp) box 319.22 262.39 315.65 522.53 433.98 484.6 736.35 779.63 1015.23 0.451756153 0.03768 0.00631429 polypeptide 54 32708 cDNA sequence BC068171 1424.91 1570.38 1471.39 2308.1 2391.78 2968.3 2287.82 2852.25 2449.75 0.585484655 0.03768 0.00081003 13654 ubiquitin-conjugating enzyme 656.86 318.47 383.2 924.15 728.47 782.62 1092.38 932.79 1270.08 0.474140955 0.03769 0.00312346 E2O 15701 proteasome (prosome, 711.54 339.67 377.73 882.09 954.28 936.36 747.49 930.36 1311.81 0.495953936 0.0377 0.00367955 macropain) subunit, beta type 4 43187 jumonji domain containing 1B 13.53 5.03 18.14 102.01 28.28 55.5 131.11 118.55 104.24 0.136004002 0.0377 0.00131957 44702 zinc finger protein 407 25.36 30.71 38.29 227.66 134.41 183.53 100.04 82.93 152.65 0.214157645 0.03772 0.00029598 14551 ribosomal protein S24 1773.15 1158.27 1610.42 2156.3 1692.91 2124.5 2913.41 2832.19 3114.02 0.61238471 0.03774 0.0206946 379 zinc finger, A20 domain 1713.11 1445.5 1218.63 2269.6 2150.04 2173.5 2659.81 2431.14 3458.7 0.578127838 0.03774 0.00444974 containing 2 20984 splicing factor, arginine/serine- 2351.06 1787.06 1796.58 3052.8 2627.08 2864.6 3491.69 3251.35 3629.06 0.627461802 0.03775 0.00349604 rich 1 (ASF/SF2) 17472 amine oxidase, copper 69.46 19.83 7.36 85.43 273.68 193.82 107.32 107.65 335.47 0.175190553 0.03778 0.00363781 containing 3 29573 RIKEN cDNA 4930535B03 86.18 17.31 12.72 377.01 80.79 145.39 180.67 103.3 181.19 0.217550428 0.03778 0.00481092 gene 738 ubiquitin-like 1 (sentrin) 239.75 189.44 212.92 490.87 339.53 437.9 482.8 633.06 755.85 0.408985959 0.03779 0.00153851 activating enzyme E1A 8834 solute carrier family 39 (metal 926.32 580.02 618.52 917.82 1152.33 1077.5 1430.48 1479.23 1557.51 0.558085418 0.0378 0.00688556 ion transporter), member 6 3709 guanine nucleotide binding 60.13 20.72 5.19 102.97 138.52 82.41 150.51 146.09 148.15 0.223873024 0.0378 0.00231997 protein 13, gamma 36724 interferon-induced protein 35 1116.96 271.9 305 985.49 1595.47 746.92 620.37 1621.46 1471.57 0.48112275 0.03782 0.03491781 240 minichromosome maintenance 3.51 116.93 27.29 275.96 137.29 122.81 381.1 145.29 202.31 0.233609539 0.03783 0.00879308 deficient 5, cell division cycle 12377 p53 and DNA damage regulated 1 725.38 231.39 442.6 715.57 694.98 822.93 1022.53 1047.48 1095.64 0.5183687 0.03784 0.01170324 12147 scaffold attachment factor B2 121.67 55.05 141.82 202.46 205.91 445.2 256.47 382.54 338.31 0.34796192 0.03785 0.00328657 11762 activating transcription factor 7 225.98 243.54 179.98 629.85 458.47 542.77 416.46 320.25 530.93 0.448127283 0.03785 0.00146075 interacting protein 2 1985 protein kinase, AMP-activated, 41.91 31.4 14.25 149.26 132.45 140.8 117.68 165.53 217.77 0.189628475 0.03786 9.79E−005 gamma 1 non-catalytic subunit 924 solute carrier family 1 (neutral 10.9 13.02 15.54 68.86 61.47 39.47 135.13 217.53 154.55 0.116571395 0.03787 0.00095526 amino acid transporter), member 5 12998 splicing factor, arginine/serine- 665.47 668.28 445.98 808.48 849.06 987.04 1495.44 1250.6 1317.15 0.530647294 0.03789 0.00796067 rich 1 (ASF/SF2) 22322 drebrin-like 16.85 15.82 9.22 61.28 99.35 52.2 236.1 101.96 127.64 0.123472801 0.0379 0.00042543 23370 RNA binding motif protein 3 39.43 20.38 13.54 161.7 136.81 113.63 64.65 102.43 161.88 0.197948995 0.03791 0.00037432 15912 MBD2-interacting zinc finger 391.59 235.52 209.12 595.63 489.39 563.7 600.44 667.79 618.68 0.473030266 0.03793 0.0007328 21512 makorin, ring finger protein, 1 1072.98 807.82 1014.98 1919.8 1380.03 1377.3 1555.19 1824.23 2003.22 0.575718958 0.03793 0.00309783 18256 cofactor required for Sp1 478.92 496.91 461.96 789.66 829.56 748.74 1285.92 1020.77 1061.21 0.501333715 0.03794 0.0015605 transcriptional activation, subunit 2 18900 GTP binding protein 4 1225.17 664.56 760.91 1492.5 1158.36 1447.9 2173.69 1808.18 1582.59 0.548608423 0.03795 0.00801715 29040 expressed sequence AA673488 484.11 218.8 155.21 630.18 425.47 677.11 680.05 395.77 933.82 0.458593416 0.03796 0.01368159 5392 Pbx/knotted 1 homeobox 136.46 110.17 38.04 161.58 245.89 197.24 309.66 326.55 315.1 0.36589504 0.03796 0.00483993 21315 importin 7 1897.13 1382.87 1447.66 2615.2 2037.98 2474.9 2454.84 2754.77 2633.6 0.631563479 0.03798 0.00311793 29563 cDNA sequence BC068171 663.48 885.66 893.34 1434 1361.4 1572.1 1455.55 1492.34 1452.45 0.557143297 0.038 0.00034246 15723 centromere protein E 638.18 667.92 635.85 1062.6 840.39 1209.8 1570.6 1201.87 1244.4 0.544756305 0.03801 0.00298774 14383 eukaryotic translation initiation 20.96 15.05 9.7 81.27 106.34 102.48 124.36 76.5 147.21 0.14325561 0.03802 1.95E−005 factor 5B 10833 eukaryotic translation initiation 88.55 23.79 36.88 226.1 76.88 140.2 208.42 168.48 203.88 0.291456698 0.03803 0.00358346 factor 3, subunit 9 (eta) 657 FK506 binding protein 4 880.01 451.63 640.66 1073.2 846.29 1012.7 1672.69 1558.58 1505.66 0.514345769 0.03803 0.01132742 30138 anti-Mullerian hormone type 2 144.16 58.14 204.59 277.7 226.3 364.45 492.22 340.87 636.14 0.34811437 0.03803 0.00675705 receptor 20815 phosphatidylinositol transfer 80.4 58.16 113.91 393.06 254.86 712.53 266.43 91.96 256.22 0.255658056 0.03804 0.01559053 protein, cytoplasmic 1 6603 integrin alpha 6 593.83 573.74 427.75 925.3 1185.71 1056.8 971.42 1090.26 915.58 0.519219472 0.03807 0.0004221 12382 EBNA1 binding protein 2 939.3

650.84 646.44 1300.7 865.58 1123.9 1609.43 1404.18 1650.05 0.562392505 0.038 0.01050595 5650 transmembrane protein 49 178.72 95.35 104.83 304.43 188.62 201.94 473.19 397.83 447.36 0.376383874 0.038 0.00693338 16338 proteasome (prosome, 230.23 131.35 156.94 402.72 255.26 414.95 581.6 681.86 363.66 0.384080354 0.03814 0.00393859 macropain) subunit, beta type 2 9656 PRP4 pre-mRNA processing 299.22 98.41 149.09 561.48 546.09 598.99 669.75 360.25 512.38 0.45966992

0.03815 0.00313005 factor 4 homolog B (yeast) 21930 transcription factor-like 5 (basic 21.09 38.28 22.9 250.91 115.79 62.22 136.62 119.48 296.43 0.167649906 0.03819 0.00144596 helix-loop-helix) 21395 guanine nucleotide binding 226.37 103.26 158.36 279.05 215.92 341.37 489.8 485.86 609.01 0.403129272 0.0382 0.01001628 protein (G protein), beta polypeptide 2 like 1 484 Sec61 alpha 1 subunit (S. cerevisiae) 2767.22 1784.91 2139.4

3540.

2633.86 3422.7 3549.86 3286.01 3718.6

0.66413151

0.03822 0.00962031 41081 RIKEN cDNA 2700023E23 383.97 263.74 193.02 576.37 466.4 578.03 626.96 633.72 924.84 0.441754766 0.03826 0.00216237 gene 22751 RE1-silencing transcription 2083.8 1792.43 1660.4 2301.8 2518.88 2548.3 3491.19 3525.95 3353.07 0.624228963 0.03827 0.00982946 factor 6782 Ribosomal protein L41 2170.73 1455.5 2121.76 2890.9 2673.78 2954.3 3287.73 3064.33 3459.93 0.627133956 0.03827 0.00351568 23799 PRP4 pre-mRNA processing 139.76 105.45 114.11 272.96 233.13 303.29 299.62 458.97 563.81 0.337107957 0.03828 0.00127622 factor 4 homolog (yeast) 5220 guanylate cyclase activator 1a 1137.82 874.49 1002.71 1303.4 1212.1 1554.2 2394.16 2176.13 2314.5 0.550467392 0.03829 0.01816163 (retina) 22682 gb: BB204543 101.6 39.07 67.86 262.21 64.78 123.41 308.26 237.22 438.68 0.290723288 0.03833 0.02815887 /DB_XREF = gi: 8869496 /DB_XREF = BB204543 /CLONE = A430058H10 /FEA = EST /CNT = 1 /TID = Mm.215042.2 /TIER = ConsEnd /STK = 0 /UG = Mm.215042 /UG_TITLE = ESTs 7211 ADP-ribosylation factor 4 228.83 119.48 108.04 327.09 279.11 307.49 457.63 425.84 551.85 0.388546664 0.03833 0.00201733 2543 galactosidase, alpha 273.94 147.47 118.3 418.22 369.57 248.33 523.01 438.32 654.08 0.407093263 0.03834 0.00570311 19658 cDNA sequence BC021395 585.54 403.84 321.3 781.58 616.26 679.87 1012.69 951.38 1013.92 0.518495955 0.03834 0.00493793 27841 BTAF1 RNA polymerase II, B- 28.85 6.86 11.93 42.58 39.42 232.36 46.01 239.9 187.23 0.120990476 0.03834 0.00833485 TFIID transcription factor- associated, (Mot1 homolog, S. cerevisiae) 30576 Transcribed locus 510.18 377.24 438.04 946.62 823.44 1198.9 651.44 766.79 926.47 0.498886833 0.0384 0.00188992 29457 WD repeat domain 46 218.17 112.46 94.73 408.68 196.3 309.16 631.99 252.45 611.74 0.352948986 0.0384 0.01177698 19166 solute carrier family 39 (zinc 46.7 42.22 31.16 170.36 69.43 62.77 295.72 198.68 333.58 0.212429458 0.03846 0.01086785 transporter), member 4 43448 TatD DNase domain containing 1 77.05 76.25 15.42 213.53 120.79 170.2 248.59 156.85 449.66 0.248186993 0.03846 0.00550496 6729 YY1 transcription factor 283.21 139.65 276.18 630.7 488.31 503.98 593.02 531.08 482.62 0.432880971 0.03853 0.00073673 3998 procollagen, type V, alpha 3 33.3 2.46 6.94 108.05 51.77 59.8 243.66 175.36 95.74 0.11628857 0.03853 0.00187396 14394 acetyltransferase 2 315.87 400.24 148.72 745.68 497.68 1107.4 690.17 601.4 547.17 0.412858906 0.03864 0.00534374 4785 RIKEN cDNA 2410016F19 2626.86 1700.7 1801.16 2574.1 2660.57 2995.8 4101.89 3403.46 3437.85 0.639284686 0.03864 0.01416184 gene 19007 GTP binding protein 3 315.42 126.56 117.97 465.37 336.42 416.21 408.64 480.29 597.69 0.414069259 0.03872 0.00246244 7933 protein regulator of cytokinesis 1 717.27 432.74 439.28 852.9 910.14 799.31 1102.98 1075.94 1372.07 0.519941636 0.03905 0.0038711 18762 RIKEN cDNA 1810003N24 844.39 363.6 396.78 978.22 773.69 906.85 985.65 1181.43 1314.69 0.522681267 0.0394 0.00727294 gene 10372 IMP4, U3 small nucleolar 1079.23 720.29 726.16 1229.9 1160.97 1507.8 1381.36 1559.21 2228.6 0.557065661 0.03946 0.00884479 ribonucleoprotein, homolog (yeast) 41173 gb: BB209183 496.81 534.73 672.17 964.31 1013.34 1068.5 823.07 1042.47 1568.62 0.525809642 0.03951 0.00333501 /DB_XREF = gi: 8874136 /DB_XREF = BB209183 /CLONE = A430091G17 /FEA = EST/CNT = 18 /TID = Mm.129698.1 /TIER = Stack /STK = 17 /UG = Mm.129698 /UG_TITLE = ESTs 15338 RAB20, member RAS oncogene 486.8 419.24 302.02 593.19 602.78 611.39 1207.04 970.25 1217.61 0.46443661 0.03951 0.01195215 family 15902 Crx opposite strand transcript 1 216.2 196.78 180.31 438.71 365.54 284.88 517.72 489.36 491.37 0.458567465 0.03955 0.00125293 13638 ribosomal protein S21 2584.81 1818.73 2032.86 3125.7 2859.55 3137.7 3666.04 3359.24 5278.12 0.600791827 0.03957 0.0123343 7634 cyclin M2 191.94 160.39 185.32 529.15 281.25 348.56 414.53 418.85 581.74 0.417741484 0.03961 0.00131644 3158 GATA binding protein 4 243.29 314.72 216.04 548.17 372.29 460.72 660.84 563.02 829.97 0.450682822 0.03963 0.00324729 14053 denticleless homolog 117.57 78.14 95.78 349.89 205.74 183.08 336.21 206.1 338.68 0.359930851 0.03967 0.0011816 (Drosophila) 21575 tubulin, beta 5 38.96 56.74 38.01 155.85 185.38 153.18 142.88 165.48 195.42 0.267904908 0.03967 1.01E−005 1352 peptidylprolyl isomerase D 707.11 447.21 263.78 1140.3 699.01 928.31 1030.22 754.1 902.76 0.519960034 0.03969 0.00795448 (cyclophilin D) /// lysosomal- associated membrane protein 3 /// similar to peptidylprolyl isomerase D 17069 autophagy-related 3 (yeast) 314.5 241.22 433.46 642.61 635.28 677.38 1423.01 439.15 1211.18 0.393420846 0.03973 0.01356134 20883 RIKEN cDNA 2900053A13 46.21 35.31 27.79 124.96 115.95 155.72 172.07 129.07 221.68 0.237772581 0.03978 6.40E−005 gene 12626 dipeptidase 3 414.84 426.47 469.53 773.35 660.61 710.24 1012.53 968.29 930.73 0.518554122 0.03979 0.00111782 24211 zinc finger protein 292 14.9 34.16 12.24 99.79 76.57 80.72 137 132.44 131.78 0.186237278 0.03985 0.00012921 10640 kelch-like 22 (Drosophila) 63.35 36.5 154.28 373.75 196.24 394.95 84.02 140.12 513.75 0.29847959 0.03988 0.03136841 5230 von Hippel-Lindau syndrome 242.32 87.46 145.37 415.71 238.33 239.9 369.93 417.03 500.62 0.435613701 0.03994 0.00838939 homolog 12058 ring finger protein (C3H2C3 554.18 420.14 401.07 655.12 583.25 868.77 1096.24 908.12 1006.93 0.537426516 0.03997 0.0070928 type) 6 10617 sarcolemma associated protein 102.17 105.27 51.27 194.14 150.33 224.98 300.15 333.64 268.15 0.351653878 0.04 0.00175258 39100 nucleolar protein 9 340.36 166.21 323.61 458.72 342.33 403.84 935.22 768.76 875.51 0.438740296 0.04 0.02347893 1097 homeodomain interacting 11.81 29.62 9.18 120.44 57.72 112.28 96.61 68.27 152.13 0.166630998 0.04003 0.00030594 protein kinase 3 13562 cDNA sequence BC010304 1318.59 952.75 1281.75 1970.4 1624.18 2021.9 1486.9 2242.25 2206.77 0.615126394 0.04003 0.00682695 7422 H3 histone, family 3A 878.81 631.98 853.13 1174.7 1128.36 1357.7 1349.45 1593.59 2334.29 0.528957723 0.04006 0.00865031 16942 SUMO/sentrin specific 2271.54 1602.51 1721.79 2780.1 2659.11 2911.5 2929.1 2911.41 3250.48 0.641664431 0.04006 0.00238324 peptidase 3 21171 ribosomal protein L29 /// 1696.19 634.99 1377.16 1987.6 2266.44 1883.6 1592.12 2337.53 4074.9 0.524436456 0.04009 0.02917422 hypothetical protein LOC669999 /// similar to 60S ribosomal protein L29 18445 Yip1 domain family, member 4 782.63 357.97 422.77 943.49 888.23 831.02 1009.32 1081.25 1031.26 0.540531103 0.04011 0.00347794 23583 CXXC finger 6 166.09 59.38 58.14 251.54 278.86 292.88 369.76 167.47 233.69 0.355802283 0.04012 0.00239894 11104 RAN binding protein 5 1214.6 825.31 930.44 1439.4 1397.73 1332.6 1951.59 1977.64 2086.45 0.583253563 0.04015 0.00776708 20617 placenta specific 9 196.43 91.79 72.6 352.41 222.51 218.3 278.58 511.3 340.48 0.37515466 0.04017 0.00430094 2867 tumor necrosis factor receptor 301.25 159.52 151.05 479.97 246.27 564 471.44 369.03 575.57 0.452148336 0.0402 0.00844923 superfamily, member 12a 16007 hypothetical LOC435970 /// 678.45 317.43 184.75 688.24 630.48 750.43 1021.21 760.72 1173.03 0.469985729 0.04022 0.01029519 similar to gonadotropin inducible ovarian transcription factor 2 38800 Glutamine fructose-6-phosphate 154.6 86.66 72.39 201.4 144.57 299 425.52 262.91 388.13 0.364385169 0.04027 0.00670534 transaminase 1 13746 deoxyhypusine synthase 40.12 11.88 30.86 40.89 74.65 90.18 175.94 258.31 230.1 0.190465245 0.04028 0.0095116 12807 peptidyl prolyl isomerase H /// 48.4 49.08 49.99 166.67 194.54 121.42 198.1 204.78 97.2 0.300129234 0.04032 0.00035827 hypothetical protein LOC624822 /// similar to Peptidyl-prolyl cis-trans isomerase H (PPIase H) (Rotamase H) 13130 protein 102.04 67.67 139.68 333.55 151.31 287.34 230.45 274.04 374.05 0.374850067 0.04033 0.00283292 2362 cofilin 2, muscle 978.51 785.68 989.09 1233.6 1142.57 1301.9 2052.78 1861.5 1865.78 0.582208806 0.04038 0.01428345 6144 eukaryotic translation initiation 106.88 47.69 39.81 160 100.21 135.61 343.08 263.59 456.25 0.266503969 0.04038 0.00981135 factor 4E member 2 14010 eukaryotic translation initiation 630.83 605.07 661.68 984.87 922.28 1001.4 1288.76 1369.41 1283.35 0.554029868 0.04039 0.00170399 factor 5B 17195 ariadne homolog 2 (Drosophila) 1041.91 675.07 711.19 1533 934.55 1369.8 1554.44 1033.03 1685.49 0.598785251 0.04042 0.01816852 38383 mitochondrial ribosomal protein 1289.27 719.43 948.29 1789.4 1403.2 1559.5 1291.59 2038.19 1795.1 0.598760357 0.04043 0.00896259 S6 16985 mitochondrial ribosomal protein 192.78 74.48 65.23 382.08 203.89 182.76 355.09 320.19 281.17 0.385455431 0.04046 0.00469527 L39 2261 mitochondrial ribosomal protein 11.28 52.99 34.16 169.89 124.95 91.91 119.25 152.47 153.1 0.242566877 0.04049 0.00084464 L39 39073 phosphatidylinositol 3-kinase, 76.55 96.39 113.73 271.48 148.58 263.12 289.7 255.76 314.46 0.371550774 0.0405 0.00077467 catalytic, beta polypeptide 5910 proteasome (prosome, 774.34 476.98 629.32 1287.5 896.48 1249 1056.77 933.88 1219.72 0.566167074 0.0405 0.00346014 macropain) 26S subunit, non- ATPase, 14 38875 RIKEN cDNA 1110008B24 723.82 473.87 306.58 908.37 546.03 872.14 1023.54 1117.82 1343 0.517740797 0.04052 0.01875828 gene 44707 expressed sequence AF013969 143.57 109.96 108.78 314.91 203.78 285.29 503.61 242.43 417.29 0.36833036 0.04052 0.00212647 /// similar to CG5514-PB, isoform B /// region containing expressed sequence AF013969; RIKEN cDNA A230054D04 gene 8041 ring finger and WD repeat 1896.6 1829.31 1380.91 2772 2658.21 3056.3 2072.36 2195.33 2804.08 0.656477432 0.04054 0.01044825 domain 3 28154 methyltransferase like 2 51.31 48.28 45.52 144.77 183.34 169.06 101.31 165.95 286.78 0.276081849 0.04056 0.00042431 30269 nucleolar protein 11 29.76 6.59 11.32 94.82 98.86 59.84 176.47 125.5 88.54 0.148036582 0.04058 0.00033177 7189 valosin containing protein /// 441.58 368.14 517.63 943.18 758.44 743.25 937.83 818.51 891.57 0.521267363 0.04058 0.0004249 similar to Transitional endoplasmic reticulum ATPase (TER ATPase) (15S Mg(2+)- ATPase p97 subunit) (Valosin- containing protein) (VCP) 16306 ubiquitin specific peptidase 10 257.9 263.88 466.98 838.32 498.36 592.08 738.05 449.15 994.08 0.481143736 0.04059 0.0102128 24333 activating transcription factor 7 998.36 673.13 860.25 1461.8 1354.64 1323.4 1579.88 1425.89 1629.02 0.577057117 0.0406 0.00102143 interacting protein 2 18466 host cell factor C1 217.35 291.13 173.2 369.82 317.79 306.44 711.47 663.73 675.05 0.447840226 0.04061 0.01723647 7354 hippocampus abundant gene 392.76 231.65 210.52 490.55 398.57 461.1 662.98 750.7 838.3 0.463566709 0.04063 0.00703408 transcript 1 11196 eukaryotic translation initiation 795.82 790.01 913.29 1492.1 1297.24 1320.6 1521.77 1501.26 1366.38 0.588076665 0.04065 0.00040865 factor 4, gamma 1 12088 pyridoxal (pyridoxine, vitamin 341.59 275.6 123.17 435.93 526.52 455.27 643.14 513.95 833.89 0.434394344 0.04067 0.0051941 B6) kinase 955 eukaryotic translation initiation 3497.53 2343.31 2333.08 3666.5 3233.57 3908.4 5268.73 4157.74 4381.74 0.664095243 0.0407 0.01798116 factor 3, subunit 10 (theta) 21792 Zinc finger protein 444 311.39 109.74 33.14 452.64 198.57 309.81 294.53 537.31 689.29 0.36602945 0.0407 0.01990646 2633 WD repeat domain 33 130.08 90.77 188.21 291.14 355.77 593.08 234.78 271.81 596.3 0.349194154 0.04072 0.00518948 16350 complement component 1, q 1157.96 830.97 657.36 1662.1 1312.42 1366.6 1453.75 1506.64 2023.78 0.567554294 0.04074 0.00450461 subcomponent binding protein 16278 RIKEN cDNA 2610524G07 445.79 163.3 359.19 701.15 580.47 1519.9 587.27 478.76 1412.36 0.366776895 0.04075 0.0187662 gene 41375 core-binding factor, runt 362.76 159.53 39.4 549.54 295.88 488.83 219.51 745.72 448.33 0.408827393 0.04076 0.02903456 domain, alpha subunit 2, translocated to, 2 homolog (human) 9888 vitelliform macular dystrophy 2- 26.77 68.92 92.66 159.89 205.9 333.32 240.53 128.6 182.61 0.301155214 0.04079 0.0025478 like protein 1 12466 ribosomal protein S24 1501.15 1020.57 1349 1942.8 1498.52 1804.5 2346.82 2369.96 2625.8 0.614966159 0.04082 0.01377549 6758 zinc finger protein 143 70.96 68.45 69.67 183.06 92.13 284.13 176.81 250.89 303.16 0.324109814 0.04085 0.0039866 23587 GTPase activating protein and 333.58 155.43 192.66 424.38 502.98 467.39 685.61 645.29 353.59 0.442752108 0.04086 0.00362749 VPS9 domains 1 12738 type 2B 125.53 76.26 48.2 253.24 181.84 235.81 167.98 240.57 313.04 0.359057222 0.04087 0.00119569 14480 Son cell proliferation protein 352.01 285.74 318.7 532.78 480.48 448.55 821.48 910.68 792.96 0.479792723 0.04088 0.00694346 11012 SET translocation 915.35 704.29 595.07 1259.9 1330.58 1160.7 1068.77 1370.79 1550.02 0.572220299 0.04088 0.00220896 2866 tumor necrosis factor receptor 320.47 172.16 158.2 480.91 257.13 582.58 497.84 384.37 599.54 0.464485418 0.0409 0.00962175 superfamily, member 12a 38041 sorting nexin 6 279.12 83.74 111.89 319.18 284.78 562.5 346.75 388.99 594.39 0.380318755 0.0409 0.00500672 13631 protein tyrosine phosphatase- 221.52 140.45 439.19 494.52 549.29 538.97 573.99 612.57 1361.41 0.387900502 0.04091 0.00955865 like A domain containing 1 40666 bromodomain and PHD finger 123.25 66.62 84.15 270.72 241.5 263.39 137.62 214.11 397.32 0.359450632 0.04092 0.00275523 containing, 3 25023 cyclin M4 81.3 61.69 90.14 148.79 264.46 223.53 165.53 233.02 314.14 0.345513424 0.04095 0.00066368 15839 peroxisome proliferator 3.63 2.38 10.41 65.58 38.61 88.28 38.4 118.58 104.52 0.072339582 0.04096 0.00013507 activated receptor binding protein 14494 DnaJ (Hsp40) homolog, 183.48 163.99 62.66 294.14 274.02 311.49 605.82 320.93 536.74 0.350068711 0.04097 0.00463062 subfamily B, member 12 10865 xylulokinase homolog (H. influenzae) 570.91 332.39 251.87 818.91 532.81 562.41 921.59 711.51 946.94 0.514074901 0.04101 0.00971793 16446 Unc-51 like kinase 1 (C. elegans) 688.42 447.89 387.79 998.96 689.04 942.76 783.34 1059.4 1087.82 0.548107284 0.04102 0.00483918 12517 PRP38 pre-mRNA processing 453.67 395.38 239.57 654.65 564.35 746.42 1167.03 624.92 806.21 0.477090355 0.04103 0.0054774 factor 38 (yeast) domain containing B 12358 DEAH (Asp-Glu-Ala-His) box 72.27 61.52 54.09 167.12 149.31 199 299.91 175.4 477.91 0.255854016 0.04106 0.00156953 polypeptide 40 13777 general transcription factor III C1 161.54 193.59 135.49 406.5 272.1 321.91 350.92 440.43 553.06 0.418453508 0.04108 0.00119698 1549 spermatogenesis associated 5 119.35 125.19 136.28 318.86 254.39 257.63 387.86 321.28 353.57 0.402220122 0.04111 0.000123 7228 activity-dependent 454.34 277.92 262.38 806.44 487.17 695.53 665.1 564.28 782.06 0.497247899 0.04113 0.00268655 neuroprotective protein 17344 glutamine fructose-6-phosphate 374.81 257.95 316.1 699.57 464.92 769.86 656.51 363.82 746.9 0.51267837 0.04113 0.0111343 transaminase 1 22765 purine rich element binding 155.98 78.28 45.27 264.07 195.74 234.5 347.63 237.43 304.74 0.352917411 0.04118 0.00165563 protein B 2822 FUS interacting protein (serine- 2250.39 1979.57 1833.46 2877.6 2467.65 3105.4 3470.04 3149.84 3432.49 0.65539575 0.04119 0.00493355 arginine rich) 1 29854 ADP-ribosylation factor-like 15 102.07 159.07 161.91 336.3 397.43 326.19 521.65 339.7 306.09 0.379866748 0.04131 0.00035486 14013 DEAD (Asp-Glu-Ala-Asp) box 388.08 161.92 274.42 654.08 454.68 714 468.82 637.43 504.22 0.480259115 0.0414 0.00404719 polypeptide 52 44759 expressed sequence AA763515 8.75 107.57 93.59 266.69 476.12 367.11 115.8 208.23 76.04 0.278028331 0.04145 0.03222834 25723 nucleolar protein 9 814.25 472.11 250.05 1027.7 836.53 843.91 990.85 1023.2 913.87 0.545203243 0.04161 0.00953711 19626 sestrin 2 492.49 377.96 378.76 576.84 439.85 945.27 773.15 957.31 978.1 0.534934012 0.04167 0.02023325 17889 phosphatidylinositol 4-kinase 199.31 230.48 234.25 466.28 327.46 508.52 589.11 402.49 715.19 0.441361892 0.04173 0.0022702 type 2 beta 24760 RIKEN cDNA 4933402C05 526.44 324.33 277.42 582.5 656.43 516.22 821.01 823.62 1015 0.511096816 0.04177 0.00786959 gene 40677 RIKEN cDNA D530033C11 62.8 31.87 92.29 229.92 169.71 276.49 176.84 152.21 205.02 0.308976276 0.04182 0.00070361 gene 40756 cDNA sequence BC057371 266.3 343.51 142.19 489.41 461.09 497.84 765.56 698.43 524.25 0.437644402 0.04183 0.00285669 15702 ribosomal protein S17 3413.68 2189.66 2823.31 4101 3483.88 3592.5 4611.75 4168.53 4913.62 0.677620117 0.04188 0.01435464 16556 nuclear import 7 homolog (S. cerevisiae) 1117.61 701.46 924.84 1468.6 1454.75 1208.1 1615.11 1894.95 1641.93 0.591138237 0.04193 0.00457958 11703 poly (A) polymerase alpha 15.3 45.46 34.26 129.02 144.67 119.25 158.08 76.86 140.95 0.247180781 0.04198 0.0004212 5457 homeodomain interacting 982.38 849.34 1301 1736.4 1266.8 1727.8 1609.86 1888.44 2141.79 0.604126672 0.04203 0.00752055 protein kinase 1 21337 carboxypeptidase D 52.84 88.41 40.22 258.05 184.47 187.52 155.3 168.61 253.58 0.300563961 0.04209 0.00026393 21183 ubiquitin associated protein 2- 704.73 268.76 278.2 1175.1 736.68 781.12 765.49 711.76 1019.45 0.48238121 0.04214 0.00655066 like 16501 eukaryotic translation initiation 1962.76 1345.41 1507.34 2379.6 1854.13 2427.1 3453.2 2549.07 3057.45 0.612638481 0.04218 0.01453233 factor 3, subunit 10 (theta) 791 Morf4 family associated protein 1 1393.96 988.45 1124.79 1873 1359.87 1748.1 1989.43 2140.18 2023.47 0.629994243 0.04224 0.00786029 9218 protein arginine N- 1192.36 520.85 617.17 1347.3 1072.8 1130.9 1415.39 1423.29 1354.94 0.601806934 0.04277 0.01108551 methyltransferase 6 39489 RIKEN cDNA 2610206G21 385.68 426.03 475.42 734.42 556.38 887.02 879.79 778.82 850.91 0.549194212 0.04282 0.00202463 gene 14334 WD repeats and SOF domain 431.5 295.6 235.2 806.65 558.06 634.33 784.95 603.44 597.88 0.482923537 0.04287 0.00128243 containing 1 24209 RIKEN cDNA 2610020H08 32.11 23.32 52.07 145.28 75.19 165.2 243.85 127.48 115.24 0.246491791 0.04302 0.00099377 gene 20784 DEAD (Asp-Glu-Ala-Asp) box 70.39 42.43 116.81 234.66 140.44 219.65 270.65 147.92 253.11 0.362641441 0.04305 0.00237097 polypeptide 10 7934 protein regulator of cytokinesis 1 882.29 561.67 562.14 1130.7 990.99 915.08 1248.9 1220.25 1392.55 0.581610598 0.04307 0.00476743 8707 zinc finger, CCCH-type with G 51.69 25.13 56.62 118.43 68.27 140.57 216.62 178.11 256.1 0.272855536 0.043 0.00395268 patch domain 21424 ubiquitin specific peptidase 36 186.19 106.7 198.3 424.4 291.16 431.35 322.19 484.24 311.35 0.433790055 0.04312 0.0015881 7817 signal peptide peptidase 3 87.29 42.07 37.9 188.55 124.22 96.45 188.49 216.63 182.01 0.335745471 0.04317 0.00179556 22171 stathmin-like 3 280.8 139.85 201.65 475.25 288.43 374.17 564.11 475.36 454.23 0.472953202 0.04321 0.00392245 20309 cofactor required for Sp 1 401.97 260.33 241.18 724.75 562.78 486.97 470.51 624.15 970.19 0.470642166 0.04322 0.00490214 transcriptional activation, subunit 7 1349 RIKEN cDNA 0610009D07 161.97 142.69 83.83 332.41 184.17 281.59 388.71 302.32 482.73 0.394020072 0.04326 0.00393886 gene 10566 CUG triplet repeat, RNA 368.59 320.29 329.52 818.02 671.83 693.42 734.46 490.43 505.7 0.520406964 0.04332 0.00216732 binding protein 1 8579 cell cycle progression 1 220.05 202.83 244.27 519.44 428.94 471.56 477.1 413 524.9 0.470662518 0.04333 8.49E−005 15916 BTB and CNC homology 1 299.52 142.08 280.99 509.03 500.69 370.86 552.06 427.69 703.89 0.471630627 0.04338 0.00429197 4645 nucleolar protein 7 551.77 243.19 360.68 894.12 728.94 555.6 772.7 534.61 874.95 0.529998257 0.04348 0.00928765 29317 NIMA (never in mitosis gene a)- 692.79 642.8 418.9 917.15 746.99 927.21 1171.25 1253.89 1243.99 0.560496959 0.04353 0.00770205 related expressed kinase 2 11419 tropomyosin 3, gamma 574.31 530.72 522.22 1153.2 848.47 1058.4 816.32 879.3 1247.36 0.542146497 0.04358 0.0016093 1594 NIMA (never in mitosis gene a)- 750.07 650.55 453.52 1026.9 842.77 1001 1176.28 1304.61 1168.12 0.568777283 0.04363 0.00385126 related expressed kinase 2 23285 RIKEN cDNA 1110004B13 32.86 16.77 16.39 47.07 45.2 114.19 120.64 162.14 140.35 0.209723788 0.04369 0.00294454 gene 8141 FUS interacting protein (serine- 657.7 606.69 401.25 1289.5 963.26 940.8 1005.18 1015.79 962.73 0.539283789 0.04379 0.0014819 arginine rich) 1 694 heme oxygenase (decycling) 2 228.15 127.34 175.71 429.17 306.91 318.12 522.16 364.93 537.19 0.428649818 0.0438 0.0018308 21921 WD repeat domain 33 423.94 236.64 225.43 650.55 442.71 521.71 588.06 600.77 812.98 0.489944094 0.04384 0.0034789 23670 BRF2, subunit of RNA 101.79 131.02 195.54 374.57 304.79 715.04 381.23 100.11 630.97 0.341762709 0.04385 0.05104204 polymerase III transcription initiation factor, BRF1-like 29502 transmembrane protein 39b 176.13 81.2 214.01 384.29 398.39 485.44 203.27 287.14 367.76 0.443344981 0.04389 0.00918906 17866 caspase 3 628.36 670.27 458.61 1113.9 883.27 1268.1 856.19 1204.37 987.32 0.556689339 0.0439 0.00269251 21277 ribosomal protein L23 4511.51 3680.37 3884.36 5456.7 5071.7 5720.7 6020.5 5596.08 6154.6 0.709944642 0.04396 0.00538158 6830 N-acetylated alpha-linked acidic 977.43 735.87 1119.53 1576.5 1513.42 1599.2 1649.89 1277.79 1688.28 0.608881433 0.0440 0.0026034 dipeptidase 2 14469 growth arrest specific 2 296.03 215.2 25.66 413.0 244.06 357.68 862.42 415.16 513.27 0.382727402 0.044 0.02873344 12046 RIKEN cDNA 2610304G08 258.49 114.73 87.48 371.57 264.27 368.45 247.09 401.41 444.6 0.439307902 0.04412 0.00518255 gene 688 EMG1 nucleolar protein 747.94 398.7 373.77 892.83 714.84 908.61 952.79 986.65 1139.24 0.543492715 0.04414 0.00487152 homolog (S. cerevisiae) 12472 phosphoribosyl pyrophosphate 1491.3 1292.29 865.49 1886.3 1875.57 1977.5 2339.73 2006.58 1731.57 0.617588445 0.04415 0.005014 amidotransferase 6656 solute carrier family 30 (zinc 297.02 228.45 223.91 509.29 464.77 462.7 542.34 536.01 601.37 0.480914365 0.04415 0.00017236 transporter), member 5 20828 survival motor neuron domain 1251.34 889.9 1044.49 1444.9 1548.98 1671.9 1831.75 1993.53 1836.28 0.616951332 0.04419 0.00303399 containing 1 1798 replication factor C (activator 1) 2 112.63 81.23 219.08 447.59 301.17 360.79 232.07 199.2 517.32 0.401274938 0.0442 0.00918665 15103 polymerase (RNA) III (DNA 722.68 439.95 880.64 968.12 883.9 1401.1 997.47 1601.38 1547.52 0.552273944 0.04421 0.01694181 directed) polypeptide A 25102 Protein phosphatase 2 (formerly 174.77 85.22 66.46 204.94 186.65 182.56 357.01 457.2 468.36 0.351641605 0.04424 0.00971819 2A), catalytic subunit, beta isoform 11003 programmed cell death 2-like 554.47 517.02 316.42 881.18 628.34 852.95 854.94 1019.81 858.95 0.544687481 0.04425 0.00361332 1176 myeloid cell leukemia sequence 1 967.2 721.92 533.68 1440.5 1391.54 1486.5 898.34 715.94 1658.09 0.585653235 0.04426 0.04611204 519 zinc finger and BTB domain 53.35 146.21 217.39 394.13 287.82 382.18 413.55 194.42 1009.27 0.310997736 0.04435 0.01661823 containing 17 7589 MYB binding protein (P160) 1a 627.85 220.85 196.3 619.81 559.46 543.97 759.99 756.52 1180.53 0.472820726 0.04436 0.01351934 15255 hexosaminidase B 452.07 322.98 329.02 829.4 691.76 686.04 625.54 661.85 990.61 0.492316954 0.04441 0.00102269 13783 5,10-methylenetetrahydrofolate 92.68 23.2 61.28 119.07 236.68 128.56 224.28 167.49 212.1 0.325607896 0.04442 0.0031695 reductase 22165 ribosomal protein S23 1550.31 917.07 1521.18 2053.3 1593.83 1798.2 2341.16 2253.28 2552.84 0.633474792 0.04442 0.01650885 1699 ELOVL family member 6, 123.87 55.45 27.87 238.32 107.52 110.47 373.69 190.73 287.91 0.316649346 0.04452 0.01238244 elongation of long chain fatty acids (yeast) 30087 RIKEN cDNA 4930515G01 30.95 26.16 15.9 110.2 64.69 112.74 138.13 116.5 168.78 0.205361161 0.04458 0.00016379 gene 9641 ankyrin repeat and MYND 67.44 57.45 75.7 180.49 149.85 218.49 301.23 86.12 363.81 0.308602374 0.04462 0.007918 domain containing 2 12034 RIKEN cDNA 1100001I22 gene 632 348.59 642.76 973.51 834.59 1122.8 900.12 946.7 1813.9 0.49254739 0.04463 0.00948749 6044 Son of sevenless homolog 1 230.34 128.95 112.01 438.22 273.17 373.78 444.95 294.97 346.44 0.43407183 0.04468 0.00166919 (Drosophila) 3604 podoplanin 129.35 118.81 88.89 294.23 216.59 222.67 344.13 264.7 548.92 0.356432817 0.04469 0.00216879 22451 heterogeneous nuclear 1641.05 1528.27 1311.2 2707.7 2502.94 2859.9 1831.48 2175.84 1879.69 0.642018685 0.04473 0.01239415 ribonucleoprotein K 8159 ribosomal protein S11 1905.1 755.25 1126.75 2116.3 1573.32 1611.4 2104.2 2067.46 2512.79 0.631950714 0.04489 0.02807283 19749 SET and MYND domain 83.2 60.13 96.49 253.0 152.74 155.94 279.3 195.61 293.15 0.360699338 0.04494 0.00109287 containing 5 18114 nucleolar and coiled-body 447.22 412.6 479.77 809.13 599.42 798.12 1127.99 790.66 1288.01 0.494922719 0.04504 0.00517173 phosphoprotein 1 21966 ring finger protein 7 978.6 679.37 530.73 1504.8 910.25 1298.1 1164.47 1209.11 1470.39 0.579244127 0.04509 0.00830564 33824 Rap1 interacting factor 1 1336.02 1290.49 1278.51 1985.5 1725.98 2113.1 2351.85 1874.39 2319.62 0.631344433 0.04515 0.00227917 homolog (yeast) /// similar to Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) (mRif1) 14479 solute carrier family 5 (sodium- 1025.49 706.6 869.51 1379.5 1274.12 1219.6 1518.78 1593.95 1642.94 0.602996207 0.0452 0.00271465 dependent vitamin transporter), member 6 19667 RIKEN cDNA 1500011J06 2082.92 1586.47 1424.05 2592.1 2138.83 2584.9 3671.38 2264.15 2862.89 0.632167509 0.04561 0.01397112 gene 21211 protein tyrosine phosphatase- 488.96 206.07 471.03 602.68 571.37 650.06 818.59 878.21 1244.5 0.489384964 0.04566 0.01423314 like A domain containing 1 20126 expressed sequence AA408296 1123.36 793.87 596.32 1599.9 1397.86 1490.4 981.23 1241.52 1475.94 0.614046445 0.04591 0.0132658 20457 splicing factor, arginine/serine- 2421.27 1796.6 1659.9 2947.2 2521.55 2808.5 3148.99 2942.53 3230.58 0.667956494 0.04596 0.00568803 rich 1 (ASF/SF2) 5056 synaptosomal-associated protein 749.26 643.08 613.45 1161.8 1012.37 1087.2 1424.69 1123.3 1276.51 0.566141158 0.04602 0.00087345 23 23156 peptidylprolyl isomerase 304.9 357.27 348.55 845.83 673.8 668.59 562.18 556.37 635.42 0.51277082 0.04607 0.00062062 (cyclophilin)-like 1 14444 AT rich interactive domain 4B 54.11 86.93 51.53 199.78 154.66 258.1 146.18 272.78 173.72 0.319559914 0.04675 0.00042303 (Rbp1 like) 979 fibrillarin 527.33 324.24 338.18 693.11 444.03 799.63 1106.82 681.18 990.6 0.50462636 0.04681 0.01468203 14590 RIKEN cDNA 4732471D19 51.05 36.62 123.36 196.47 132.63 198.82 195.08 238.56 382.09 0.314114539 0.04688 0.0029813 gene 2168 PWP1 homolog (S. cerevisiae) 253.54 123.82 124.06 398.21 231.41 365.55 410.58 364.75 416.54 0.458537567 0.04691 0.00338099 11080 ATP-binding cassette, sub- 147.69 158.88 142.97 345.18 164.53 215.87 707.42 447.31 892.23 0.324280263 0.04693 0.03515947 family F (GCN20), member 1 19751 ankyrin repeat and MYND 3.72 28.84 6.61 112.14 69.74 61.26 111.73 38.77 117.79 0.153178343 0.04696 0.00113502 domain containing 2 14756 Kruppel-like factor 9 210.02 29.37 90.94 354.82 272.53 212.2 254.78 274.03 358.42 0.382596509 0.04698 0.00747019 15073 YTH domain family 1 215.69 353.03 190.75 634.54 438.28 329.92 608.02 420.79 788.44 0.471721962 0.04701 0.01026759 27459 RNA pseudouridylate synthase 35.48 20.56 13.51 94.07 113.99 134.1 103.42 130.55 442.34 0.136577415 0.04707 0.00101169 domain containing 3 182 Trk-fused gene 784.41 340.53 295.58 928.5 564.98 679.38 871.81 1022.58 1079.02 0.552058093 0.04717 0.02052607 16390 cell division cycle 2 homolog A 1520.87 991.88 1873.5 1922.5 2470.74 2908.9 2019.67 2007.39 3556.92 0.589307355 0.0472 0.02144756 (S. pombe) 2140 claudin 6 377.34 362.31 248.66 836.91 293.71 421.11 822.38 709.62 736.86 0.517359884 0.04722 0.04780535 23988 RIKEN cDNA 2210011C24 72.37 81.79 46.68 176.2 192.27 212.67 138.15 189.52 394.55 0.308188068 0.04725 0.00136374 gene 14006 La ribonucleoprotein domain 423.27 344.14 388.76 594.63 701.46 735.35 726.67 737.66 830.55 0.534481962 0.04727 0.00036524 family, member 5 8270 insulin-like growth factor 2 434.23 266.75 433.37 781.98 500.48 705.3 745.85 596 939.69 0.53139859 0.04738 0.0059995 receptor 15878 zinc finger protein 289 81.46 122.04 76.07 252.08 206.46 182.53 595.85 231.71 743.7 0.252738063 0.04741 0.00831163 27919 casein kinase 1, epsilon 10.44 8.6 20.89 54.93 27.16 86.67 149.6 94.28 120.88 0.14968511 0.04752 0.00167154 3281 ubiquitously expressed 138.54 90.92 30.95 203.48 182.02 211.77 247.35 247.04 374.41 0.355249067 0.04754 0.0043143 transcript 16269 RIKEN cDNA 5730403B10 77.47 94.8 164.04 275.16 166.89 142.51 330.15 361.39 315.31 0.422656638 0.04759 0.01185988 gene 13417 IBR domain containing 3 1392.62 1504.44 1813.39 2414 2004.88 2264.8 2704.73 2941.42 2367 0.641018401 0.04762 0.00504366 23624 protein phosphatase 1A, 690.04 292.96 486.52 859.53 850.37 1201.6 707.21 1015.61 891.22 0.531900954 0.04765 0.00698808 magnesium dependent, alpha isoform 10324 caspase 3 74.65 40.81 90.44 109.36 153.83 190.24 284.59 203.65 344.59 0.320153002 0.0477 0.00417898 17368 RB1-inducible coiled-coil 1 901.84 849.94 864.96 1457.9 1313.88 1382.7 1641.67 1296.45 1849.88 0.585240717 0.04772 0.00145884 40892 Smg-7 homolog, nonsense 670.82 509.13 594.16 909.72 935.57 910.25 1666.94 1373.11 1068.38 0.516934078 0.04777 0.00541515 mediated mRNA decay factor (C. elegans) 14699 low density lipoprotein receptor- 75.98 47.15 136.94 150.37 243.04 316.66 208.78 258.74 221.87 0.371671931 0.0478 0.00218354 related protein associated protein 1 9696 protein phosphatase 1A, 281.46 111.9 158.2 565.15 304.18 544.53 369.01 388.93 396.41 0.429528738 0.04783 0.00343167 magnesium dependent, alpha isoform 12475 DEAD (Asp-Glu-Ala-Asp) box 278.5 119.19 117.37 431.43 222.53 267.29 496.73 357.89 488.83 0.454868194 0.04785 0.0119792 polypeptide 10 12733 UTP11-like, U3 small nucleolar 1652.37 1247.73 876.11 2092.8 2024.87 1852.2 1938.24 1738.63 2374.9 0.62823646 0.04788 0.00801569 ribonucleoprotein, (yeast) 16773 ribosomal protein L36a-like 2127.47 1381.86 1791.81 2318 2118.29 2209.7 3314.32 3112.02 3538.96 0.638255937 0.04798 0.02608004 28991 phospholipase C, delta 4 138.83 132.49 147.63 335.85 224.94 209.08 437.46 324.88 403.75 0.432808529 0.04808 0.0029441 8894 solute carrier family 25 207.47 125.99 152.31 472.41 322.97 339.68 379.28 255.45 490.21 0.429884956 0.04813 0.00168341 (mitochondrial carrier, phosphate carrier), member 25 12544 small nuclear RNA activating 209.56 210.89 181.97 483.56 393.07 376.22 534.26 381.24 455.1 0.459257847 0.0483 0.00019626 complex, polypeptide 3 21985 ribosomal protein S24 1695.18 1059.62 1483.47 2021.2 1554.34 1896.5 2472.65 2477.22 2756.87 0.643194644 0.0484 0.02471089 7941 MOB1, Mps One Binder kinase 559.19 330.53 241.51 736.04 605.17 626.58 639.84 1041.82 1058.44 0.480567728 0.04846 0.00718575 activator-like 1B (yeast) 7576 SWI/SNF related, matrix 431.94 141.49 156.2 467.97 379.07 430.91 503.05 853.05 827.37 0.421578427 0.04851 0.01096394 associated, actin dependent regulator of chromatin, subfamily c, member 1 3178 poly A binding protein, 1067.51 748.21 815.73 1481.8 1078.86 1271.7 1876.97 1398.42 2496.99 0.547952194 0.04868 0.01791445 cytoplasmic 1 535 proteasome (prosome, 683.88 672 512.62 1128.4 1099.82 764.78 900.56 1120.79 1147.58 0.606465831 0.04873 0.00532769 macropain) subunit, beta type 7 10969 jumonji domain containing 1A 120.68 130.02 130.27 359 253.12 231.81 183.78 364.53 594.57 0.383499177 0.04874 0.00763501 23568 BAT2 domain containing 1 1319.8 1222.06 1121.76 2051.9 1915.46 1889.3 2016.68 1664.87 1912.55 0.639891151 0.04878 0.00118966 20689 eukaryotic translation initiation 873.2 655.24 823.56 1212.8 1067.32 1162.7 1408.93 1473.86 1531.6 0.598688079 0.04879 0.00311329 factor 2, subunit 1 alpha 13607 expressed sequence AU014645 1511.34 1084.22 1023.43 1777.7 1571.13 1910.8 1920.8 1977.06 2014.19 0.647889341 0.04882 0.00448388 10857 heterogeneous nuclear 1632.02 1042.99 1052.83 1963.8 1558.88 1934.4 1928.28 2260.45 2173.42 0.630807682 0.04884 0.00723852 ribonucleoprotein M 16722 WD repeat domain 12 55.39 143.68 73.22 227.44 175.28 219.03 230.08 395.68 302.9 0.351249024 0.04887 0.0019824 3863 mitogen activated protein kinase 1. 192.12 80.19 241.96 690.93 358.51 359.34 325.02 315.25 558.26 0.394483203 0.04889 0.00710119 29078 RIKEN cDNA D330037H05 1816.97 1506.16 1606.86 2248.8 2319.28 2211 2969.76 2795.29 2623.9 0.65004971 0.04892 0.00408689 gene /// similar to La-related protein 4 (La ribonucleoprotein domain family member 4) 10770 proteasome (prosome, macropain) 97.46 73.58 87.82 238.69 150.72 194.9 269.55 209.28 386.58 0.357117236 0.04893 0.00134467 26S subunit, ATPase 2 22147 ERO1-like (S. cerevisiae) /// 1617.14 815.67 1036.5 1391.6 1541.45 2086.7 1682.06 2068.83 2407.9 0.62070841 0.04895 0.02270587 ribosomal protein L31 14175 Sec61 alpha 1 subunit (S. cerevisiae) 1726.8 1072.28 1292.76 2085.2 1791.82 2048.5 2261.11 2116.35 2459.79 0.641215536 0.04899 0.00585437 22705 ets variant gene 5 505.73 222.21 367.1 690.41 565.33 752.06 668.44 1034.4 639.83 0.503412275 0.049 0.00575794 16198 t-complex protein 1 1790.6 1179.11 1413.64 2167.2 1848.4 2128.3 2997.31 2246.75 2828.77 0.61664846 0.04902 0.01018077 20029 cDNA sequence BC024969 39.51 47.41 37.05 94.02 167.9 143.54 230.28 67.15 149.97 0.290715944 0.04904 0.00244613 6054 eukaryotic translation initiation 752.35 559.3 604.82 1247.6 942.02 997.47 1342.47 1152.54 1009.05 0.572833831 0.04905 0.00183039 factor 2, subunit 3, structural gene X-linked /// similar to eukaryotic translation initiation factor 2, subunit 3, structural gene X-linked 21965 similar to PRAME family member 8 2409.02 1514.52 1777.52 2919.6 2279.5 3009.7 2492.54 2865.6 3135.81 0.682651308 0.04905 0.01414262 /// expressed sequence AU018829 7639 nucleolar protein 11 103.2 75.19 118.35 278.21 178.97 208.17 352.34 374.83 213.44 0.369548432 0.04907 0.0014996 14311 expressed sequence C78212 421.11 232.74 227.15 553.16 581.34 405.68 580.26 619.3 637.51 0.521726257 0.04909 0.003325 7266 ubiquitin-conjugating enzyme E2B, 527.65 343.53 429.59 890.61 526.22 809.78 736.6 884.92 789.17 0.56100317 0.0491 0.00503997 RAD6 homology (S. cerevisiae) 11354 Mus musculus, clone 72 27.43 24.72 143.74 119.31 60.58 222.57 201.82 145.95 0.277749813 0.04912 0.00430038 IMAGE: 3983419, mRNA 10003 RNA guanylyltransferase and 5′- 106.94 84.63 87.19 301.26 182.18 150.86 353.53 154.09 362.86 0.370499342 0.04914 0.00611854 phosphatase 1462 exosome component 5 40.73 61.74 17.43 87.19 68.73 139.55 145.69 246.81 177.61 0.277039673 0.04916 0.00522601 8293 ring finger and SPRY domain 633.65 573.63 579.76 1137.8 1373.91 1161.8 843.63 923.02 883.55 0.565188996 0.04916 0.00324511 containing 1 8271 insulin-like growth factor 2 74.29 195.52 490.69 528.54 492.61 528.94 459.73 649.21 498.88 0.481647672 0.04917 0.01382869 receptor 8020 pleckstrin homology domain containing, 625.38 324.51 341.8 1052.9 850.6 998.02 505.77 626.89 737.95 0.54134623 0.04918 0.01741884 family F (with FYVE domain) member 2 39491 zinc finger protein 710 727.55 440.46 524.24 900.66 784.47 1074.7 975.36 1333.25 979.43 0.559617585 0.04919 0.00456617 1486 DnaJ (Hsp40) homolog, 2390.47 1648.72 1910.19 2935.8 2556.3 2981.4 2867.17 2942.9 3211.21 0.68013085 0.0492 0.00549139 subfamily B, member 9 15093 ribosomal protein S17 2459.15 1443.18 2004.58 2845.5 2446.97 2579.6 3506.76 2970.35 3555.66 0.659810063 0.0492 0.0169152 2115 torsin family 1, member B 256.19 89.29 93.92 278.8 251.82 363.38 456.6 304.99 408.7 0.425715379 0.04921 0.00453646 27418 cDNA sequence BC035295 443.69 439.27 554.8 570.76 834.16 708.51 1041.56 1097.16 911.05 0.556925937 0.04922 0.00861834 17466 G patch domain containing 4 560.23 265.59 219.67 798.37 518.64 726.56 747.62 528.15 616.45 0.531273264 0.04923 0.00884928 2013 eukaryotic translation initiation 271.74 95.04 221.24 323.99 248.6 395.58 465.04 463.27 611.39 0.468939778 0.04924 0.01506929 factor 3, subunit 4 (delta) 27189 RIKEN cDNA E430025E21 155.47 124.82 115.94 304.08 355.62 222.62 391.26 261.61 311.02 0.429236111 0.04925 0.00055666 gene 7846 mannosidase, alpha, class 2C, 6.08 8.03 3.61 38.99 14.56 85.09 59.15 145.44 156.62 0.07090127 0.04928 0.00203805 member 1 15948 ATPase type 13A3 1601.83 1562.47 1794.92 2141.2 2094.83 2038.2 3190.74 2860.13 3084.85 0.643639106 0.0493 0.01688862 3056 insulin-like growth factor 2 mRNA 23.6 23.13 59.05 86.87 175.53 124.87 113.81 134.37 168.17 0.263258754 0.0493 0.00046644 binding protein 1 31866 M-phase phosphoprotein 1 584.18 393.46 472.99 807.12 805.27 884.71 916.93 822.02 1167.48 0.536919384 0.04933 0.00130358 11154 growth factor, erv1 (S. cerevisiae)- 390.69 114.24 604.44 777.64 571.65 1161.3 360.32 727.15 1012.77 0.481198735 0.04935 0.04517723 like (augmenter of liver regeneration) 4640 cyclin M3 240.03 342.07 62.47 256.37 380.42 457.8 470.6 681.96 476.52 0.473309909 0.04937 0.02795838 12184 phosphatidylinositol transfer 70.98 70.85 77.64 242.87 150.65 236.21 204.73 89.26 219.98 0.383789455 0.0494 0.00477932 protein, cytoplasmic 1 16753 COX4 neighbor 595.77 603.5 354.09 995.56 953.48 706.37 894.23 725.76 1113.09 0.576547419 0.04941 0.00769649 8770 TruB pseudouridine (psi) 1598.35 788.01 714.92 2065.6 1575.69 1737.5 1380.01 1601.91 1777.98 0.611769533 0.04943 0.01407303 synthase homolog 2 (E. coli) 35301 gb: AV268519 446.43 227.18 224.84 668.78 557.23 627.97 642.03 432.62 473.25 0.528207932 0.04945 0.00529613 /DB_XREF = gi: 16389684 /DB_XREF = AV268519 /CLONE = 4930535J16 /FEA = EST /CNT = 4 /TID = Mm.38413.1 /TIER = ConsEnd /STK = 2 /UG = Mm.38413 /UG_TITLE = ESTs 11455 cDNA sequence BC010304 237.84 308.43 345.14 374.3 548.32 431.79 1196.49 751.72 656.51 0.450306002 0.04951 0.02034917 14840 ERO1-like (S. cerevisiae) /// 1914.61 1048.97 1332.05 1815.1 1860.89 2459.7 2005.25 2401.75 2725.53 0.647509527 0.04952 0.01837773 ribosomal protein L31 16309 prion protein 5.67 27.92 7.5 114.55 67.49 114.67 39.64 77.22 93.19 0.162167495 0.04953 0.00068104 7219 proliferation-associated 2G4 3806.66 2690.44 2523.5 4149.4 3627.73 3863 4934.86 4376.47 4773.38 0.701316785 0.04956 0.01729256 22327 proteasome (prosome, 310.97 225.94 272.82 597.48 410.26 388.07 523.64 561.2 597.35 0.52614035 0.04956 0.00218884 macropain) subunit, alpha type 4 17151 exonuclease 3″-5″ domain-like 2 69.67 29.49 42.91 151.69 68.29 135.72 157.58 233.27 169.66 0.310125408 0.04957 0.00330747 10743 sorbitol dehydrogenase 167.8 89.01 200.21 398.11 251.14 352.86 403.04 323.86 301.79 0.450088635 0.04957 0.00219161 6064 nuclear receptor coactivator 6 1342.43 996.25 1101.97 1935.4 1486.31 1789.3 1893.95 2042.34 1527.18 0.64464665 0.04958 0.00539514 interacting protein 14546 exocyst complex component 8 38.13 48.15 41.87 130.42 147.06 97.95 144.96 178.44 148.81 0.30236893 0.04961 4.94E−005 14589 RIKEN cDNA 4732471D19 gene 50.72 36.59 43.82 139.69 116.02 153.6 151.77 176.54 113.67 0.308073629 0.04963 3.73E−005 17331 ribosomal protein L15 1103.58 552.38 1197.41 1368.2 1136.31 1371.7 1675.87 2054.56 2318.95 0.574953378 0.04963 0.02851657 29240 catenin (cadherin associated 55.32 151.05 51.37 125.57 252.74 142.05 216.39 309.83 274.46 0.390207715 0.04966 0.00867468 protein), delta 1 8570 expressed sequence AI840826 48.97 43.58 48.65 146.36 99.71 108.05 225.48 172.99 158.23 0.310050284 0.04967 0.00041891 29169 RNA binding motif protein 4 177.47 100.66 79.8 250.81 194.96 248.25 310.54 382.4 312.05 0.421339486 0.04967 0.00235887 40440 RIKEN cDNA C130032F08 1581.36 805.74 827.62 1302.8 1329.25 1510.7 2220.74 2011.87 2336.34 0.600228723 0.0497 0.03109115 gene 18873 basic leucine zipper and W2 1856.21 1429.11 1724.42 2392.9 2189.52 2377.5 2784.24 2571.65 2854.64 0.660457255 0.04971 0.00401185 domains 1 13899 karyopherin (importin) beta 1 30.07 36.79 45.53 113.82 67.63 72.13 158.24 180.43 197.68 0.284556859 0.04972 0.00325133 18692 GA repeat binding protein, 1521.21 896.36 993.48 1692.9 1670.86 1806.1 2042.84 1734.73 2022.7 0.621877894 0.04976 0.00459458 alpha 42681 activating signal cointegrator 1 complex 300.81 273.13 256.77 436.29 426.49 352.72 661.15 697.71 694.37 0.508276915 0.04976 0.00901142 subunit 3 7056 solute carrier family 22 (organic 78 127.98 90.24 109.02 174.7 301.99 259.41 365.4 248.19 0.406139671 0.04977 0.01328366 anion/cation transporter), member 12 2136 peroxisomal membrane protein 2 28.37 71.63 15.47 123.16 112.33 103.51 137.14 245.59 211.62 0.247431296 0.0498 0.00176646 12220 histone aminotransferase 1 95.59 63.13 63.73 206.98 126.57 201.1 258.49 221.04 202.13 0.365775454 0.0498 0.00050866 12258 splicing factor, arginine/serine-rich 1 1549.68 1176.89 1231.71 2058.8 1861.02 1951.5 1990.71 2140.9 2193.12 0.649106926 0.0498 0.00186597 (ASF/SF2) 12983 PAK1 interacting protein 1 75.66 34.9 47.76 190.93 119.37 100.33 294.26 127.72 233.4 0.297030074 0.0498 0.00310024 12327 ribosomal protein L31 1611.89 822.9 1110.43 1525.1 1520.0 1916.3 1780.17 2157.72 2472.13 0.62353448 0.0498 0.01946329 14684 heterogeneous nuclear 1389.69 888.32 1178.26 1690.06 1425.06 1871.4 1956.12 2275.22 1706.98 0.632700133 0.0498 0.00961426 ribonucleoprotein A1 21465 translocase of outer mitochondrial 1215 813.02 1005.8 1760.6 1492.51 1269.6 1678.31 1498.07 2176.74 0.614391051 0.04982 0.00941987 membrane 20 homolog (yeast) 13601 guanine nucleotide binding 627.77 328.73 461.31 838.59 772.45 739.06 836.66 835.1 1505.97 0.512971636 0.04985 0.00920993 protein-like 3 (nucleolar) 25426 DNA segment, Chr 5, Wayne State 31.53 65.26 42.32 176 76.21 139.61 139.72 309.45 160.76 0.277733966 0.04985 0.00304201 University 178, expressed 22109 RIKEN cDNA 2700007P21 563.57 337.22 396.2 764.62 661.9 636.46 1052.76 777.27 896.81 0.541561061 0.04986 0.00415005 gene 34705 uroporphyrinogen decarboxylase 312.94 195.7 307.86 802.17 395.61 379.25 967.5 396.14 683.09 0.450636908 0.04986 0.02054484 3486 homeodomain interacting 514.46 276.53 265.41 530.11 301.61 663.23 1201.72 793.58 994.76 0.471080332 0.04986 0.05047199 protein kinase 3 23671 polycomb group ring finger 5 728.53 398.49 398.87 916.23 850.34 1205.5 787.59 737.65 933.74 0.561910338 0.04986 0.00662276 3870 zinc finger protein 292 61.98 31.99 50.41 71.7 60.09 122.44 175.23 148.97 187.23 0.333572072 0.0499 0.00486358 1959 N-myc downstream regulated 19.32 37.3 32.34 163.21 83.33 51.59 232.87 162 63.09 0.235315902 0.04991 0.00686013 gene 3 21127 coiled-coil domain containing 132.83 55.7 44.7 210.48 136.27 157.44 194.19 308.63 357.29 0.341904273 0.04991 0.00496129 86 7468 trans-golgi network protein 504.95 301.85 270.73 671.72 450.68 487.94 700.65 843.07 702.27 0.558837029 0.04991 0.01315788 4093 component of oligomeric golgi 747.08 426.75 620.57 928.72 864.53 976.28 1190.49 1078.38 2087.76 0.503609237 0.04995 0.01527683 complex 4 19091 phosphoserine aminotransferase 1 962.82 668.17 307.26 1569 751.88 888.84 1338.76 947.09 1617.53 0.544979622 0.04995 0.03781093 7812 ATPase, Na+/K+ transporting, 47.24 70.25 39.58 362.38 201.58 163.49 145.12 138.2 113.32 0.279461609 0.04995 0.0017652 alpha 1 polypeptide

indicates data missing or illegible when filed

TABLE 9A Row Gene CycA2.1 CycA2.2 CycA2.3 NI1.1 NI1.2 NI1.3 NI2.1 NI2.2 NI.2.3 FoldChange R MeanFDR T 8013 Rasl11b: RAS-like, family 11, 1175.28 1162.12 866.08 67.51 155.4 83.97 28.63 67.32 76.13 13.37793368 0 0.013333333 281.069 member B 16505 Gyg: glycogenin 2774.07 3647.22 2911.43 451.38 788.3 545 633.2 808.2 736.02 4.71113938 0 0.036666667 146.474 44280 Gyg: glycogenin 2716.28 3189.75 2680.95 587.38 955.1 642.4 640.7 735.8 665.37 4.063169251 0 0.046666667 115.459 19189 Hsbp1: heat shock factor binding 2054.28 1787.07 1312.02 326.46 423.8 376.3 415.9 610.1 588.56 3.760019554 0 0.056666667 88.0219 protein 1 38879 0610008C08Rik /// LOC621156 574.74 794.44 810.38 108.25 279.7 167.9 96.73 84.66 122.89 5.068037018 0 0.044285714 82.2657 /// LOC631337: RIKEN cDNA 0610008C08 gene /// hypothetical LOC621156 /// hypothetical protein LOC631337 21617 Ywhab: tyrosine 3- 1175.16 1329.81 1339.93 250.85 326.1 341.3 285.4 335.3 415.3 3.935031906 0 0.045 79.1967 monooxygenase/tryptophan 5- monooxygenase activation protein, beta polypeptide 12776 Gpsn2: glycoprotein, synaptic 2 960.08 781.16 213.63 107.93 146.7 123.1 160.8 174.9 137.46 4.595531107 0 0.043333333 75.6419 38623 Rgs2: regulator of G-protein 963.98 951.57 378.04 252.29 232 224.9 47.94 265.8 134.38 3.963622853 0 0.041666667 72.6641 signaling 2 14769 Ywhab: tyrosine 3- 984.18 1329.73 1254.81 241.01 312 348.2 323.2 330.1 398.25 3.654921319 0 0.043333333 69.7329 monooxygenase/tryptophan 5- monooxygenase activation protein, beta polypeptide 21642 Tax1bp3 /// Rpl13: Tax1 (human 1245.68 2205.53 913.44 382.12 394.4 282.3 507.1 145.2 438.71 4.060385047 0 0.041666667 68.3463 T-cell leukemia virus type I) binding protein 3 /// ribosomal protein L13 22387 BC018601: cDNA sequence 871.11 1011.02 988.69 262.99 239.9 197.1 251.4 209.6 269.45 4.013785582 0 0.041555556 67.9884 BC018601 28288 Zfp291: zinc finger protein 291 987.39 413.21 165.77 31.66 208.2 60.95 9.02 50.48 51.43 7.609463431 0 0.038333333 65.2239 15663 Ninj1: ninjurin 1 768.76 910.41 1337.77 236.5 145 273.4 260.1 211.1 352.74 4.080392223 0 0.037121212 60.0212 27398 Zar1: zygote arrest 1 196.34 550.87 430.24 96.91 62.32 61.6 36.14 73.34 105 5.409708024 0 0.0376 56.505 8065 Hsbp1: heat shock factor binding 1479.03 1221.16 1148.4 399.02 455.2 495.6 385.2 442.7 494.47 2.880433196 0.0222222 0.053111111 42.8537 protein 1 20436 Gltscr2: glioma tumor suppressor 229.4 345.29 561.03 117.87 44.11 14.4 87.12 56.32 105.97 5.334648536 0.0227273 0.054166667 42.8606 candidate region gene 2 10123 Hspb1: heat shock protein 1 451.26 233.48 504.65 36.78 60.45 103.9 181.6 70.72 133.05 4.055475996 0.0232558 0.054263566 43.1189 32039 Myo5b: myosin Vb 932.01 832.86 419.75 166.98 224 201.3 246.4 398.8 209.84 3.018911206 0.025641 0.057435897 43.5021 19373 Mtap: methylthioadenosine 430.05 544.69 232.61 76.62 179.7 135.6 24.53 69.42 68.87 4.352771519 0.0263158 0.05877193 43.6173 phosphorylase 15861 Ptk9l: protein tyrosine kinase 9- 3879.84 515.28 668.16 278.34 548 167.5 39.25 201.2 238.1 6.87782117 0.027027 0.053873874 45.4725 like (A6-related protein) 5039 Ywhab: tyrosine 3- 786.43 1401.89 1268.98 550.3 550.1 542.5 548.9 344.8 534.84 2.251344699 0.0275229 0.057889908 31.9962 monooxygenase/tryptophan 5- monooxygenase activation protein, beta polypeptide 7118 Zfp313: zinc finger protein 313 664.63 959.1 606.33 102.21 233.1 60.95 260.6 238.4 243.17 3.917884751 0.0277778 0.052314815 45.8903 27301 Chsy1: carbohydrate (chondroitin) 3606.66 3856.21 3309.81 1920.1 1952 1650 1778 2224 1984.7 1.872169743 0.0283019 0.058207547 32.1594 synthase 1 23482 Wdr51b: WD repeat domain 51B 549.71 635.29 186.24 78.52 121.3 128.3 70.8 228.5 105.47 3.74236511 0.0285714 0.052857143 46.074 22475 Sept11: septin 11 379.67 680.28 606.49 144.25 278.7 239.7 234.4 123.4 131.01 2.894758327 0.0288462 0.05875 32.2155 16314 2700060E02Rik: RIKEN cDNA 1657.64 2133.91 1718.85 759.77 1151 666.9 740.4 552.1 918.56 2.301557302 0.0291262 0.05776699 32.463 2700060E02 gene 40450 Pfdn4: prefoldin 4 835.74 1351.12 1275.03 465.73 482.3 379.6 367.1 416.9 416.99 2.738241285 0.0294118 0.052941176 46.429 3542 Rgs2: regulator of G-protein 910.45 1375.3 511.1 289.77 380.2 277.6 309.3 389.5 287.36 2.89283424 0.0294118 0.05622549 37.2147 signaling 2 38514 Prkaca: protein kinase, cAMP 1061.04 1151.27 898.98 699.13 230.1 414.1 446.6 245.9 459.58 2.493540321 0.0294118 0.058267974 32.4698 dependent, catalytic, alpha 9746 Ptprj: protein tyrosine 313.63 348.74 149.56 38.69 84.77 85.95 59.83 36.02 100.14 4.005574741 0.029703 0.058778878 32.499 phosphatase, receptor type, J 21697 Zfp313: zinc finger protein 313 3162.11 3960.29 3102.1 1059.1 1648 1223 1678 2090 1792.6 2.154513004 0.0298507 0.054328358 37.9163 19162 Gtf2b: general transcription factor 952.55 1437.02 1358.53 532.39 552.3 466.5 425.1 572.2 544.43 2.423695714 0.030303 0.05479798 37.9814 IIB 5038 Ywhab: tyrosine 3- 842.81 1251.66 740.5 218.36 255.6 347.1 475.5 409.7 250.61 2.897586852 0.030303 0.058754209 32.6829 monooxygenase/tryptophan 5- monooxygenase activation protein, beta polypeptide 16058 Gm428 /// LOC623180 /// 1730.14 2814.61 2209.92 718.98 1302 938 1086 1344 986.94 2.118852909 0.0309278 0.059450172 32.7088 LOC623197 /// LOC623210 /// LOC623219: gene model 428, (NCBI) /// hypothetical LOC623180 /// hypothetical LOC623197 /// hypothetical LOC623210 /// hypothetical LOC623219 1904 Ube2a: ubiquitin-conjugating 835.58 1090.31 1082.16 322.75 424.9 331.9 208 371.1 379.5 2.9516296 0.03125 0.053854167 46.9047 enzyme E2A, RAD6 homolog (S. cerevisiae) 1431 Srpk2: serine/arginine-rich protein 1149.91 1761.01 1427.58 473.26 698.9 399.7 966.1 423.3 728.78 2.351516006 0.03125 0.06 32.7117 specific kinase 2 11264 2610510J17Rik: RIKEN cDNA 957.03 1024.23 729.2 175.1 254.7 235.5 303 296 462.73 3.138886637 0.0322581 0.054086022 47.3645 2610510J17 gene 16336 Uchl1: ubiquitin carboxy-terminal 1255.01 1792.27 1364.58 298.99 536.1 340.2 818.6 772.9 910.66 2.399366965 0.0325203 0.061382114 30.5168 hydrolase L1 16195 Bpgm: 2,3-bisphosphoglycerate 1084.63 1316.44 933.03 223.6 542.2 298.2 441 450.4 441.04 2.78256733 0.0327869 0.055846995 38.5724 mutase 15069 2700060E02Rik: RIKEN cDNA 1911.39 1978.28 1849.47 866.04 1267 698.8 686.8 853.4 876.63 2.186763905 0.032967 0.058608059 33.4602 2700060E02 gene 1378 Sec61b: Sec61 beta subunit 629.4 1333.69 789.37 274.35 516.3 341.2 201.2 346.8 199.6 2.929224024 0.0330579 0.061019284 30.716 277 Herpud2: HERPUD family 1579.89 1939.26 1921.14 868.46 883.8 596.7 827.7 1099 877.44 2.11163511 0.0333333 0.059185185 33.4759 member 2 22096 Mm.69144.1 453.06 395.64 858.44 130.38 120.9 231.2 100.7 88.48 177.73 4.019684715 0.0337079 0.057453184 33.9669 28335 Usp27x: ubiquitin specific 1037.34 637.29 144.44 150.48 158.3 218 119.3 163.4 242.26 3.459491841 0.0338983 0.056384181 39.0302 peptidase 27, X chromosome 1111 Nek7: NIMA (never in mitosis 717.12 574.95 336.93 210.68 267.8 172 134 130 199.51 2.924911121 0.0338983 0.060988701 30.8699 gene a)-related expressed kinase 7 12221 Cpa1: carboxypeptidase A1 1233.98 1187.56 1071.87 304.36 410.4 369.7 630.8 505.1 743.84 2.357067674 0.0344828 0.061005747 30.9745 10438 5830415L20Rik: RIKEN cDNA 1215.2 1852.35 1334.99 447.1 794.1 612.1 547.7 578.6 472.45 2.550718424 0.0348837 0.059224806 33.9864 5830415L20 gene 20740 Mm.27444.1 337.59 481.47 424.2 81.2 144.9 122.1 82.14 158 135.08 3.437268455 0.0350877 0.06 31.3576 6654 Hmgn1: high mobility group 2802.24 3952.07 3639.58 1578 1726 1428 2308 2200 2525.7 1.766840536 0.0357143 0.061142857 29.2973 nucleosomal binding domain 1 2773 Lmo1: LIM domain only 1 728.82 1098.32 1034.76 305.51 364.2 304 486.9 565.8 414.43 2.345012373 0.036 0.060986667 30.4439 16848 Ube2a: ubiquitin-conjugating 986.42 1081.65 857.17 294.92 401.6 308.1 491.7 435.7 385.52 2.524566112 0.0363636 0.058787879 31.7403 enzyme E2A, RAD6 homolog (S. cerevisiae) 28139 Mall: mal, T-cell differentiation 140.43 181.82 65.34 2.1 15.41 3.36 15.11 1 10.85 16.20698307 0.037037 0.058436214 34.7455 protein-like 23084 2410127E18Rik: RIKEN cDNA 526.43 815.91 633.99 308.65 278.7 283.9 152.4 171.6 168.65 2.897993299 0.037037 0.060518519 29.7435 2410127E18 gene 42427 Mrg1: myeloid ecotropic viral 1187.24 1519.64 1212.95 887.49 524.6 553.7 452.6 589.9 467.49 2.255569398 0.037037 0.063101852 25.4067 integration site-related gene 1 34813 LOC627488 /// LOC627520 /// 2997.33 4389.29 4558.04 2547.1 3079 2572 1852 2591 2371.8 1.591199861 0.0372093 0.063224806 25.4182 LOC667692 /// LOC667695 /// LOC673990: similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML- 1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML-1 and LEF-1) (Aly/REF) /// similar to THO complex subunit 4 (Tho4) (RNA and export factor binding protein 1) (REF1-I) (Ally of AML- 1 and LEF-1)(Aly/REF) 14324 2700060E02Rik: RIKEN cDNA 1736.22 1743.31 1787.5 771.81 1146 670 697.7 850.4 807.84 2.130990215 0.0373134 0.060746269 29.8051 2700060E02 gene 5988 Ak3l1: adenylate kinase 3 alpha- 923.36 955.8 444.05 293.2 479 230.4 457.2 322.9 400.3 2.128475753 0.0373832 0.063317757 25.4548 like 1 1245 Tnfaip8: tumor necrosis factor, alpha-induced protein 8 360.72 565.75 517.2 173.14 264.6 167.2 150.3 188 131.01 2.688048113 0.0375587 0.063067293 25.4969 29349 Srrm2: serine/arginine repetitive 422.76 520.49 235.84 276.19 142 111.1 23.71 54.04 95.17 3.358560971 0.0378788 0.060505051 30.0013 matrix 2 18213 Gnas: GNAS (guanine nucleotide 749.56 1054.77 1007.27 303.09 467.2 274.3 329.4 595 414.54 2.359288924 0.0381679 0.060916031 30.0133 binding protein, alpha stimulating) complex locus 12033 Zfp313: zinc finger protein 313 2750.76 3476.54 2573.42 687.45 1148 821.6 1426 1577 1289.5 2.532599515 0.0384615 0.048589744 51.0983 27637 Nr2e1: nuclear receptor subfamily 1154.42 1358.16 898.95 372.14 477.2 439.9 220.9 478.6 491.58 2.750834556 0.0384615 0.055705128 40.7351 2, group E, member 1 2211 Fxc1: fractured callus expressed 319.96 265.72 286.07 4.63 47.28 3.92 13.61 90.27 179.09 5.146103896 0.0384615 0.058162393 35.2462 transcript 1 23218 5730405I09Rik: RIKEN cDNA 1466.98 1315.46 1000.54 584.51 638.8 679.3 643.1 491.1 601.7 2.079343049 0.038835 0.062718447 25.8477 5730405I09 gene 9918 Nobox: NOBOX oogenesis 557.22 579.54 288.37 129.03 371.4 87.59 172.8 98.82 245.05 2.580168012 0.0390244 0.062520325 25.9252 homeobox 27981 1110003E01Rik: RIKEN cDNA 935.07 637 979.71 438.48 639.8 244.7 270.6 373.4 222.36 2.331073921 0.0392157 0.060915033 28.4683 1110003E01 gene 23766 4930431B09Rik: RIKEN cDNA 288.09 929.85 626.58 234.92 253.4 170 197.8 182.5 246.51 2.870446163 0.0396825 0.061349206 30.3043 4930431B09 gene 2222 Ddx19a: DEAD (Asp-Glu-Ala- 1171.65 1506.5 1210.32 497.39 638.6 587.9 581.9 501.6 556.5 2.311923278 0.0397727 0.062424242 27.0664 Asp) box polypeptide 19a 9267 BC004728: cDNA sequence 2914.05 3310.43 4063.56 1784.9 1884 1762 2063 1805 2090.6 1.80671016 0.039801 0.063034826 25.9867 BC004728 11008 Sec24b: SEC24 related gene 491.17 371.38 563.69 38.39 140.5 93.28 159.3 103.5 197.21 3.896085448 0.04 0.056866667 41.2419 family, member B (S. cerevisiae) 20332 2610510J17Rik: RIKEN cDNA 920.34 904.56 875.79 268.6 445 387.9 292.4 305.2 492.61 2.464504236 0.04 0.061555556 28.6135 2610510J17 gene 1259 Eefsec: eukaryotic elongation 420.39 175.37 131.6 27.72 33.52 41.27 19.45 30.53 65.01 6.688367816 0.04 0.062038095 27.1963 factor, selenocysteine-tRNA- specific 17879 Ehd4: EH-domain containing 4 1018.34 1327.03 1393.04 514.73 741 621.1 418.3 856.2 476.56 2.06100183 0.04 0.062966667 26.0088 7236 Snx9: sorting nexin 9 2034.25 2223.65 2179.13 937.58 906.1 769.4 1117 1452 1343 1.972975541 0.0402685 0.060939597 28.7304 19870 Ggta1: glycoprotein 2076.84 1911.12 1747.57 1033.9 1405 1131 712.7 1003 500.21 1.982372856 0.040404 0.063013468 26.0912 galactosyltransferase alpha 1, 3 4975 Ywhag: 3- 1701.12 2425.78 1962.92 1046 935.4 694.1 728.4 780.6 1139.8 2.287531271 0.0405405 0.057837838 35.922 monooxygenase/tryptophan 5- monooxygenase activation protein, gamma polypeptide 3840 Atp6v1c1: ATPase, H+ 1562.18 1993.36 1324.28 641.08 676.2 434.4 835.1 1096 751.79 2.200907908 0.0405405 0.061306306 28.7411 transporting, lysosomal V1 subunit C1 1499 Kdelr2: KDEL (Lys-Asp-Glu- 1134.97 1840.76 1296.63 454.68 740.1 649.3 505.6 898.4 565.51 2.240609193 0.0405405 0.063108108 25.1968 Leu) endoplasmic reticulum protein retention receptor 2 19039 Csda: cold shock domain protein A 1886.38 2541.08 2229.73 996.1 1299 937.6 1283 1407 1167.3 1.877663438 0.040724 0.06321267 25.2231 9095 Dnahc8: dynein, axonemal, heavy 275.09 424.82 466.62 57.34 144.7 48.48 81.76 152.8 74.6 4.169007541 0.0408163 0.054013605 41.8892 chain 8 4403 Gadd45b: Growth arrest and DNA 325.8 1088.25 1693.72 59.09 210.2 129.8 401.4 453.8 881.65 2.91008774 0.0408163 0.061360544 28.7836 damage-inducible 45 beta 23361 Fbxo28: F-box protein 28 728.16 665.63 382.02 171.44 132.3 122.3 209.7 213.5 344.89 2.974406646 0.0410959 0.056164384 36.4751 6486 G6pd2 /// G6pdx: glucose-6- 919.61 1851.91 1150.83 309.7 590.7 402 725.6 646.1 587.89 2.404866938 0.0412371 0.063487973 26.2283 phosphate dehydrogenase 2 /// glucose-6-phosphate dehydrogenase X-linked 22429 Gorasp2: golgi reassembly 1053.97 1211.58 759.04 341.93 459 419.6 583.3 420.2 553.71 2.177773618 0.0414747 0.063195084 25.3481 stacking protein 2 6921 Kif17: kinesin family member 17 1050.79 1040.1 651.51 576.54 561.7 248.7 435.1 356.1 394 2.132420979 0.0416667 0.063368056 26.3333 13584 Dcp1a: decapping enzyme 1250.95 1233.21 734.43 514.44 536.9 508.7 712.4 438.6 473.45 2.021454389 0.0418848 0.063560209 26.3363 4967 Ncoa4 /// LOC627557: nuclear 819.67 1349.74 597.1 225.35 376.4 254.5 372.8 517.1 318.51 2.679817891 0.0419162 0.06257485 27.4886 receptor coactivator 4 /// similar to nuclear receptor coactivator 4 14382 Pcid2: PCI domain containing 2 208.21 208.84 103.64 13.83 77.97 8.25 39.19 18.14 57.28 4.85129973 0.0424242 0.063030303 27.5603 9970 Csrp1: cysteine and glycine-rich 707.37 1081.76 451.86 402.09 254.6 515.3 117.8 186.2 282.36 2.54908518 0.042471 0.065933076 23.6583 protein 1 9611 Ptprj /// AW125753: protein 276.18 258.57 380.78 49.33 87.25 38.19 50.96 146.2 102.3 3.861366512 0.0425532 0.064255319 24.6082 tyrosine phosphatase, receptor type, J /// expressed sequence AW125753 12280 2610528K11Rik: RIKEN cDNA 847.62 350.15 887.05 191.27 286.5 257.4 379.5 362.4 372.64 2.254139704 0.0426829 0.063130081 27.6 2610528K11 gene 14887 Tmem109: transmembrane protein 1049.13 1100.4 693.15 487.81 701.2 347.9 350.2 365 381.93 2.158401859 0.0427807 0.064171123 26.423 109 8101 Camk2g: calcium/calmodulin- 283.06 354.25 367.2 116.66 94.65 136.1 97.12 109.2 105.92 3.04563095 0.0428016 0.065823606 23.7561 dependent protein kinase II gamma 22457 Sepw1: selenoprotein W, muscle 1 2758.54 3164.45 4104.83 1517.9 1644 1398 1870 1618 3061.9 1.805050019 0.0429688 0.065950521 23.7661 15377 Tm2d2: TM2 domain containing 2

761.31 348.95 1367.84 465.42 283.5 356.7 295.1 314.2 225.89 2.553662885 0.0431373 0.066183007 23.7726 13610 Pnrc1: proline-rich nuclear 1875.98 2497.69 2218.37 912.68 1173 1023 1143 1267 1271.5 1.9415163 0.0432099 0.063333333 27.6831 receptor coactivator 1 22912 Calcoco1: calcium binding and 645.5 564.97 318.61 259.49 280.1 113.5 190.8 154.3 163.4 2.632509534 0.0432432 0.06372973 26.5901 coiled coil domain 1 7409 Tgfb2: transforming growth 793.78 1590.37 1213.53 412.2 635.7 521.1 714.9 491.8 663.43 2.09223397 0.0433071 0.065721785 23.8689 factor, beta 2 38991 Ttll11: tubulin tyrosine ligase-like 629.88 997.15 450.48 230.82 216.8 257.8 240 375.5 152.52 2.819887748 0.0434783 0.063967391 26.5994 family, member 11 21361 Slc25a4: solute carrier family 25 609.28 302.35 741.44 237.03 343.3 259.4 201.2 188.6 100.24 2.486193413 0.0434783 0.065144928 24.6327 (mitochondrial carrier, adenine nucleotide translocator), member 4 21528 Cnn3: calponin 3, acidic 842.6 930.24 788.12 354.82 542.4 337.9 180.8 351.3 266.95 2.518163806 0.04375 0.062583333 27.9931 15242 Pofut2: protein O- 1778.35 1399.41 2187.94 882.1 1202 822.3 491.1 875.2 1214.3 1.955775711 0.0438247 0.064940239 24.0113 fucosyltransferase 2 23699 Cd164l2: D164 sialomucin-like 2 294.25 488.64 324.23 53.73 65.52 83.92 138.4 143.4 129.99 3.600624431 0.0438596 0.064809942 24.7437 37480 4930562C15Rik: RIKEN cDNA 266.99 324.53 138.98 37.48 48.81 45.36 87.04 111.8 47.11 3.868968805 0.043956 0.063791209 26.6715 4930562C15 gene 16487 Wfs1: Wolfram syndrome 1 539 852.8 431.85 108.02 256.6 262.6 278.2 201 172.7 2.851658705 0.044 0.065093333 24.0215 homolog (human) 20014 Arrb2: arrestin, beta 2 261.8 442.51 421.66 79.45 122.9 130.7 191.7 126.2 149.35 2.813975283 0.0440529 0.064375918 24.8594 33055 2700050L05Rik: RIKEN cDNA 504.87 984.48 426.53 189.02 221.1 184 321.7 177.9 178.35 3.012176811 0.0443686 0.067963595 22.5402 2700050L05 gene 408 Fkbp8: FK506 binding protein 8 590.14 427.04 302.19 164.62 241.9 117.1 99.71 136.4 185.58 2.791638014 0.0444444 0.069534392 21.8165 39254 8430429K09Rik: RIKEN cDNA 483.61 603.3 382.14 140.52 172.4 143.3 254.2 103.1 239.14 2.791278738 0.0445344 0.06560054 24.0684 8430429K09 gene 159 Bpgm: 2,3-bisphosphoglycerate 4125.5 4888.39 3943.66 2336.5 3162 2111 2186 2053 2562.9 1.798272305 0.044586 0.063078556 28.0958 mutase 1105 Mea1: male enhanced antigen 1 641.79 1052.56 800.16 373.15 443.3 291.3 373 331.2 364.96 2.291779211 0.044586 0.069522293 21.8514 38903 2600010E01Rik: RIKEN cDNA 247.28 200.25 369.05 57.76 100.1 37.76 33.32 102.2 59.89 4.175811813 0.0446429 0.064449405 24.9266 2600010E01 gene 15195 Tm2d2: TM2 domain containing 2

807.85 315.89 1436.51 527.63 320.7 388.1 290.4 286.3 252.38 2.479036756 0.0446735 0.068373425 22.5493 21185 D10Wsu102e: DNA segment, Chr 2625.46 3167.45 2893.72 1716.1 1847 1338 1962 1712 1576.6 1.711233117 0.0447284 0.069158679 21.9226 10, Wayne State University 102, expressed 4343 2410022L05Rik: RIKEN cDNA 1605.23 1541.87 1099.08 1006.1 799.1 735.3 264.5 1067 383.1 1.995685441 0.044898 0.06537415 24.1286 2410022L05 gene 12245 Dnm1l: dynamin 1-like 714.07 890.45 642.35 203.05 404.7 362.8 383.8 214.8 288.04 2.419788054 0.0449827 0.068373702 22.606 109 Atp6v1b2: ATPase, H+ 1155.57 1164.53 728.39 468.28 602.1 390.5 479.6 654.4 600.14 1.908347679 0.0450161 0.069464094 21.9365 transporting, lysosomal V1 subunit B2 41382 9230115E21Rik: RIKEN cDNA 1049.24 1705.49 1742 671.13 1012 681.8 714.7 866.2 989.16 1.822353437 0.045082 0.065560109 24.1432 9230115E21 gene 1430 Srpk2: serine/arginine-rich protein 1999.89 2326.25 2092.34 1043.1 1218 1110 1149 875.2 960.85 2.019612501 0.0451613 0.06172043 28.271 specific kinase 2 16430 G6pdx: glucose-6-phosphate 1912.61 2849.68 1863.38 787.91 1752 1060 912.4 963.3 1065.4 2.025944759 0.0451613 0.068913978 22.0228 dehydrogenase X-linked 2300 Sdhb: succinate dehydrogenase 538.02 229.97 832.03 138.81 236.8 218.7 38.77 316.8 160.01 2.883334535 0.0452675 0.065775034 24.1473 complex, subunit B, iron sulfur (Ip) 6223 Zbtb20: zinc finger and BTB 134.97 146.13 16 4.9 11.08 4.9 9.14 2.83 47.12 7.430286357 0.0452962 0.068222997 22.6625 domain containing 20 13279 Dcp1a: decapping enzyme 370.06 844.47 493.12 102.24 141.4 115.2 321.2 207.5 303.81 2.866964391 0.0453074 0.068727077 22.0548 9363 Ddx19a /// Ddx19b: DEAD (Asp- 1900.93 2603.49 1537.03 1167.2 1153 885.9 897.4 1007 1064.7 1.956903393 0.0454545 0.06739899 23.3704 Glu-Ala-Asp) box polypeptide 19a /// DEAD (Asp-Glu-Ala-Asp) box polypeptide 19b 10998 Pold3: polymerase (DNA- 1214.68 1819.91 1832.16 850.28 830.5 871 1004 1059 901.76 1.764581113 0.045614 0.068175439 22.7446 directed), delta 3, accessory subunit 18210 Lnk: linker of T-cell receptor 473.25 331.54 156.1 95.8 81.69 130.4 71.84 51.82 156.54 3.267666463 0.0456432 0.065172891 24.3452 pathways 21746 Tmem109: transmembrane protein 786.47 847.01 508.13 367.58 528.2 245.5 273.8 272.9 273.33 2.183845573 0.0457746 0.068004695 22.7842 109 16900 Ube2j1: ubiquitin-conjugating 1048.14 731.11 425.79 189.15 297.8 190.2 412.6 359 345.7 2.457827565 0.0458333 0.065013889 24.4002 enzyme E2, J1 14774 Surf4: surfeit gene 4 2026.91 2349.99 1707.51 1143.2 1323 1046 1020 1066 1054.3 1.82922382 0.0462046 0.069229923 22.1641 6591 Dbi: diazepam binding inhibitor 748.16 1411.18 1571.45 551.45 796.2 566.5 644.3 687.8 749.36 1.867435173 0.0462633 0.067793594 22.8636 916 Llgl1: lethal giant larvae homolog 1430.08 1103.73 1765.18 919.12 927.7 845 526.8 632.3 506.16 1.97334894 0.0463576 0.069392936 22.1803 1 (Drosophila) 14725 Aldh9a1: aldehyde dehydrogenase 2464.65 2087.14 1545.48 936.87 1225 1018 1310 1014 1062.2 1.857250556 0.0464135 0.065316456 24.4636 9, subfamily A1 22776 Abhd13: abhydrolase domain 1448.41 1446.62 1230.77 644.65 823 682.5 642.8 658.9 939.64 1.879049135 0.0464396 0.070846233 21.5641 containing 13 8799 Arl8a: ADP-ribosylation factor- 450.63 484.52 240.82 185.21 144.7 165.6 126.1 202.3 138.16 2.444844075 0.0465116 0.071792636 20.9911 like 8A 4729 Tcl1b3: T-cell 3067.43 4225.86 3944.03 1750.2 2137 2048 2719 3084 2461.6 1.582715554 0.0465839 0.070662526 21.5931 leukemia/lymphoma 1B, 3 8719 Pstpip1: proline-serine-threonine 133 150.18 47.71 10.97 19.4 25.08 18.91 12.49 10.27 6.814044481 0.0466667 0.069311111 22.2252 phosphatase-interacting protein 1 5059 Rab18: RAB18, member RAS 1682.03 1655.73 1019.13 929.17 817.7 742.1 723.3 1044 764.41 1.735622591 0.0467836 0.072017544 21.015 oncogene family 11799 Runx1t1: runt-related 720.19 672.38 443.2 238.13 239.4 221.5 336.5 333.9 281.49 2.224016573 0.046875 0.0708125 21.6373 transcription factor 1; translocated to, 1 (cyclin D-related) 3543 Rgs2: regulator of G-protein 871.75 1343.48 839.92 552.53 601.3 456.3 215.4 392.9 290.79 2.435178026 0.0469799 0.069519016 22.2513 signaling 2 11937 Defb8: defensin beta 8 322.3 225.13 147.33 19.16 51.47 86.7 48.97 79.85 82 3.774331115 0.0470588 0.072215686 21.0551 22002 Anapc5: anaphase-promoting 2197.5 1065.37 1661.25 652.28 960.9 647.2 1135 645.4 1044.3 1.936841774 0.0471014 0.067777778 22.9611 complex subunit 5 270 Carhsp1: calcium regulated heat 695.96 1334.14 836.29 323.58 378.2 367.8 428.5 461.3 410.2 2.419384517 0.047138 0.06959596 22.2624 stable protein 1 11459 Lhx8: LIM homeobox protein 8 915.65 1329.12 940.38 474.05 516.8 519 579.1 373.5 302.8 2.303731001 0.0471698 0.070597484 21.6799 34771 2700050L05Rik: RIKEN cDNA 83.83 110.47 358.76 26.54 30.56 15.02 19.41 28.26 5.59 8.822140692 0.0472441 0.074041995 20.0479 2700050L05 gene 412 Orc3l: origin recognition 512.79 479.04 423.31 81.65 207.6 115.3 178 144.3 323.47 2.694683525 0.0472727 0.067612121 22.9795 complex, subunit 3-like (S. cerevisiae) 8298 Rap1a: RAS-related protein-1a 1038.15 1345.27 1417.09 535.11 752.6 615 727.4 726.5 676.38 1.884757581 0.0473373 0.071577909 21.187 18549 H1f0: H1 histone family, member 0 1417.73 1021.56 619.53 522.35 740.5 456.5 358.3 405.5 425.71 2.103018928 0.0479042 0.070588822 21.3322 29960 LOC433810: similar to 689.22 717.53 441.92 260.52 343.3 371.8 226.1 240.7 301.53 2.120070873 0.048 0.072835556 20.2788 transmembrane protein SHREW1 2778 Ggta1: glycoprotein 615.11 636.67 665.46 268.83 335 231.9 263.9 175.6 342.73 2.369976637 0.048048 0.070640641 21.3411 galactosyltransferase alpha 1, 3 23726 1700010D01Rik /// MGC118250: 514.54 738.88 626.14 342.68 278.7 196.3 235.7 321 246.24 2.319556713 0.0482574 0.073038427 20.3038 RIKEN cDNA 1700010D01 gene /// similar to hypothetical protein LOC76386 12425 Zcchc3: zinc finger, CCHC 601.6 494.73 290.75 165.02 163.9 195.7 202.5 148.4 244.54 2.476795886 0.0483384 0.070956697 21.3504 domain containing 3 10133 Trim25: tripartite motif protein 25 616.96 638.71 337.03 143.65 248.1 271 339.9 229.3 207.55 2.21282094 0.0484848 0.071151515 21.3508 8706 Car10: carbonic anhydrase 10 126.12 168.15 16.02 9.61 16.81 12.12 1.76 21.12 7.68 8.98089725 0.0485075 0.067524876 23.2315 7747 Arpc4: actin related protein 2/3 1172.92 1818.6 1389.88 803.24 994.5 747.6 842.5 574.3 530.53 1.950496372 0.0485934 0.075302643 19.7699 complex, subunit 4 39091 Ches1: checkpoint suppressor 1 691.62 717.97 330.8 186.51 461.5 200.6 209.6 288.8 218.21 2.223671686 0.0486891 0.067752809 23.2316 1396 Hspa2: heat shock protein 2 1165.3 1847.21 1706.76 768.33 1326 888 653 1010 758.87 1.746794118 0.0487179 0.0752564 19.7915 43852 LOC545637 /// LOC623272 /// 3154.18 5046.7 4038.1 1861.5 3004 2393 2912 2908 2107.5 1.611845948 0.0487805 0.073486902 20.3393 LOC623281 /// LOC636750 /// LOC667780: hypothetical LOC545637 /// hypothetical LOC623272 /// hypothetical LOC623281 /// hypothetical protein LOC636750 /// hypothetical protein LOC667780 1723 Gng3: guanine nucleotide binding 939.26 1673.4 1032.44 376.96 611.2 390.9 606.5 482.2 588.54 2.385349318 0.0488722 0.067531328 23.2874 protein (G protein), gamma 3 subunit 8545 Reep2: receptor accessory protein 2 1276.5 951.38 773.57 228.14 348.3 268 801 510.5 544.43 2.223139853 0.0489297 0.07108053 21.4329 26935 Bahd1: bromo adjacent homology 496.5 645.98 493.5 200.26 217.8 255.2 202.4 244.1 139.48 2.598567276 0.0489691 0.075197595 19.8532 domain containing 1 927 Mod1 /// LOC624892 /// 998.06 922.67 686.51 467.78 580.6 523.9 272.3 372.6 349.48 2.031565455 0.0491803 0.072905282 20.4366 LOC677317: malic enzyme, supernatant /// similar to NADP- dependent malic enzyme (NADP- ME) (Malic enzyme 1) /// similar to NADP-dependent malic enzyme (NADP-ME) (Malic enzyme 1) 38626 Mfap2: microfibrillar-associated 509.37 115.67 349.24 27.37 198.3 120.4 76.61 70.93 137.03 3.089568568 0.0492308 0.071117949 21.4898 protein 2 33836 Transcribed locus 22.68 284.45 137.88 67.18 11.32 10.03 13.47 8.36 30.26 6.329256151 0.0494792 0.0740625 20.0011 13825 Plekhc1: pleckstrin homology 433.88 1351.76 1329.49 686.75 581.8 481.9 519 457 620.73 1.861357091 0.0495868 0.072901745 20.4943 domain containing, family C (with FERM domain) member 1 20764 Txn2: thioredoxin 2 417.2 626.98 484.3 144.42 244.2 113.1 228.5 145.6 295.77 2.609329521 0.0498615 0.072816251 20.5416

indicates data missing or illegible when filed

TABLE 9B Row Gene CycA2.1 CycA2.2 CycA2.3 NI1.1 NI1.2 NI1.3 NI2.1 NI2.2 NI.2.3 FoldChange MedianFDR MeanFDR T 3646 0610007P06Rik: RIKEN 53.21 84.8 297.2 251.3 275.76 304.24 515.25 489.89 705.11 0.342476048 0.04973822 0.0741274 20.0279 cDNA 0610007P06 gene 4498 0610016J10Rik: RIKEN 4.86 1.17 7.33 143.31 63.22 200.98 78.49 177.41 3.9 0.04004136 0.042105263 0.06375439 26.3724 cDNA 0610016J10 gene 21983

278.64 96.47 238.75 422.57 521.22 543.58 778.62 488.14 494.19 0.377955374 0.048632219 0.07113475 21.3759 LOC625193 /// LOC636633: RIKEN cDNA 1110005A23 gene /// similar to cytokine induced protein 29 kDa /// similar to cytokine induced 38875 1110008B24Rik: RIKEN 377.94 192.85 622.98 908.37 546.03 872.14 1023.5 1117.8 1343 0.41087267 0.044303797 0.06272152 28.0809 cDNA 1110008B24 gene 14747 1110014K08Rik /// 181.23 248.59 247.67 383.41 393.19 537.89 753.56 769.32 870.69 0.365414799 0.041666667 0.06175926 28.8862 LOC664786 /// LOC664849 /// LOC669054 /// LOC672175: RIKEN cDNA 1110014K08 gene /// hypothetical protein LOC664786 /// hypothetical protein LOC664849 /// hypothetical protein LOC669054 /// hypothetical protein LOC672175 40498 1110034A24Rik: RIKEN 43.95 64.41 50.95 319.84 238.19 282.21 220.54 188.83 248.29 0.212711129 0.034965035 0.06109557 29.101 cDNA 1110034A24 gene 23309 1600002K03Rik: RIKEN 107 59.9 245.28 683.77 429.59 346.82 750.02 281.7 595.32 0.267023406 0.033333333 0.05611111 38.745 cDNA 1600002K03 gene 41245 2010107H07Rik: RIKEN 194.12 113.48 300.45 660.66 354.66 360.51 650.65 483.92 1044.3 0.342111408 0.040816327 0.06326531 26.1485 cDNA 2010107H07 gene 12325 2310036O22Rik: RIKEN 355.44 333.42 817.17 1346.9 1033.9 1084.7 1228.3 1278.2 1731 0.391021738 0.039473684 0.05811404 35.6782 cDNA 2310036O22 gene 16489 2410016O06Rik: RIKEN 569.29 93.03 367.09 890.36 502.25 860.54 1000.8 906.94 1398.2 0.370354647 0.035714286 0.0597619 31.4657 cDNA 2410016O06 gene 15550 2510039O18Rik: RIKEN 530.8 99.11 420.85 1242.7 731.24 1077.5 660.72 895.16 784.09 0.389791149 0.044198895 0.06355433 26.7591 cDNA 2510039O18 gene 19105 2510039O18Rik: RIKEN 89.8 83.01 199.83 321.54 214.67 216.65 401.71 481.55 470.2 0.353830377 0.049450549 0.07271978 20.4938 cDNA 2510039O18 gene 35340 2600011C06Rik: RIKEN 1515.45 1353.66 1480.64 2833.1 2791.7 2941 2356.4 2682.9 2361.5 0.544860232 0.041176471 0.06201961 27.4584 cDNA 2600011C06 gene 2216 2610029G23Rik: RIKEN 572.06 520.64 750.01 1471 1141.3 1096.6 1730.3 1327.7 1092 0.46894679 0.046931408 0.06761733 22.9544 cDNA 2610029G23 gene 12846 2810409H07Rik: RIKEN 86.52 29.18 100.39 480.67 269.97 281.71 245.18 142.85 326.22 0.247440742 0.042553191 0.0643617 26.3759 cDNA 2810409H07 gene 8238 2900073H19Rik: RIKEN 211.83 95.11 192.63 574.46 220.64 424.2 345.06 612.16 561.13 0.36496265 0.044444444 0.06426667 24.9235 cDNA 2900073H19 gene 13588

573.65 184.37 288.58 996.46 770.78 953.56 685.85 734.41 780.12 0.425345141 0.045751634 0.06929194 22.0658 cDNA, RIKEN full-length enriched library, clone: A630012F14 product: unclassifiable, full insert sequence 36328 310050K21Rik: RIKEN 311.28 401.01 530.93 1030.8 761.38 1078.3 1332.5 1029.5 1510.5 0.368745523 0.036144578 0.05738956 34.6953 cDNA 3110050K21 gene 24498 3110050K21Rik: RIKEN 451.12 293.97 202.68 849.56 599.42 547.68 1108.3 684.07 839.07 0.409568423 0.043103448 0.06469828 24.629 cDNA 3110050K21 gene 23071 3300001M20Rik: RIKEN 108.79 169.76 262.21 708.72 562.73 499.17 858.23 902.18 429.21 0.27309456 0.02173913 0.05210145 42.8378 cDNA 3300001M20 gene 32215 4833426J09Rik: RIKEN 101.24 83.15 123.05 403.04 266.83 290.65 664.64 325.8 820.34 0.221874211 0.03 0.05903333 32.5436 cDNA 4833426J09 gene 41050 4930427A07Rik: RIKEN 154.04 258.9 438 462.21 493.17 756.34 822.19 1212.3 977.74 0.36026859 0.036036036 0.05921922 31.6007 cDNA 4930427A07 gene 24760 4933402C05Rik: RIKEN 184.74 248.77 343.55 582.5 656.43 516.22 821.01 823.62 1015 0.352026602 0.031578947 0.06042105 32.7419 cDNA 4933402C05 gene 23146 4933417E01Rik: RIKEN 1233.06 595.65 1580.61 2342.5 1725.8 1965.4 2559.7 2606.8 2682.4 0.491168017 0.035714286 0.05678571 34.675 cDNA 4933417E01 gene 23294 4933440H19Rik: RIKEN 222.08 110.71 164.48 490.16 293.12 477.16 332.22 512.35 433.13 0.391838118 0.049079755 0.07127812 21.4347 cDNA 4933440H19 gene 23653 5730406M06Rik: RIKEN 175.07 173.9 279.19 681.23 606.53 632.71 617.02 514.97 512.55 0.352402939 0.037593985 0.06057644 29.9153 cDNA 5730406M06 gene 39158 5730406M06Rik: RIKEN 475.1 352.64 504.28 956.32 865.18 1125.5 938.04 1078.7 754.09 0.46591231 0.047318612 0.07053628 21.7093 cDNA 5730406M06 gene 27731 5730406M06Rik: RIKEN 984.39 305.06 745.9 1521.6 1377 1419.4 1034.7 1357.1 1056.2 0.524172156 0.048192771 0.07079317 21.3436 cDNA 5730406M06 gene 27732 5730406M06Rik: RIKEN 964.44 283.46 700.66 1444 1271 1384.7 996.72 1324 1014.8 0.5241432 0.049315068 0.07291324 20.452 cDNA 5730406M06 gene 40394 A230097K15Rik: RIKEN 739.64 322.54 497.24 1135.4 943.8 714.8 1147.6 1095.1 1136.2 0.50524631 0.044871795 0.06926282 21.9347 cDNA A230097K15 gene 40844 A530082C11Rik: RIKEN 132.33 27.77 268.5 459.34 222.66 476.49 456.67 365.07 541.49 0.339926717 0.044444444 0.06285185 26.878 cDNA A530082C11 gene 13848 AA408556: expressed 171.39 60.02 172.24 295.85 310.39 421.99 454.92 383.23 796.93 0.303119051 0.044843049 0.06391629 25.0467 sequence AA408556 44961 AA591059: Expressed 56.29 33.55 46.52 130.59 70.28 207.6 293.95 193.18 298.12 0.228462286 0.044067797 0.06924294 22.3522 sequence AA591059 20263 Abcf1: ATP-binding 1565.6 1512.55 1825.57 2799.7 2379.2 2881.9 3476.5 3087.8 3006.5 0.556241255 0.038461538 0.06267628 25.7414 cassette, sub-family F (GCN20), member 1 3399 Abhd6: abhydrolase 74 36.87 87.35 553.9 326.89 296.3 593.6 167.18 618.84 0.15505865 0 0.04020833 66.0252 domain containing 6 209.56 278.43 237.36 422.75 380.61 691.33 684.84 889.36 650.71 0.390015055 0.040229885 0.06212644 27.2306 3398 Abhd6: abhydrolase domain containing 6 7228 Adnp: activity-dependent 290.38 98.62 340.91 806.44 487.17 695.53 665.1 564.28 782.06 0.364902089 0.036764706 0.06019608 29.7163 neuroprotective protein 28853 AI449441: expressed 152.43 274.6 83.3 549.74 575.03 368.81 540.27 415.64 365.12 0.362629281 0.044176707 0.06532798 24.0235 sequence AI449441 43126 AI553587: expressed 45.94 59.16 164.25 440.23 390.53 659.33 420.52 199.69 203.51 0.232819462 0.035087719 0.05421053 39.7968 sequence AI553587 27478 Alkbh1: alkB, alkylation 367.13 252.58 364.88 684.73 472.21 782.39 1187.3 1539.4 783.2 0.361366497 0.039408867 0.06277504 25.948 repair homolog 1 (E. coli) 41185 Ankrd11: ankyrin repeat 194.44 140.3 145.55 605.72 556.5 490.08 635.77 558.13 541.28 0.283567726 0.03076923 0.05533333 38.1328 domain 11 17472 Aoc3: amine oxidase, 14.01 4.63 37.83 85.43 273.68 193.82 107.32 107.65 335.47 0.102359136 0.0390625 0.06083333 30.258 copper containing 3 20486 Aspm: asp (abnormal 199.52 137.22 144.24 521.87 545.05 411.51 527.32 557.97 436.97 0.3205796 0.027777778 0.0583642 32.0107 spindle)-like, microcephaly associated (Drosophila) 43330 Aspm: asp (abnormal 158.72 62.35 100.75 406.86 421 369.44 451.38 451.4 443.97 0.252998172 0.031746032 0.0562963 38.2554 spindle)-like, microcephaly associated (Drosophila) 32443 Aspm: asp (abnormal 292.51 187.37 247.14 625.22 519.02 571.3 712.94 561.32 557.81 0.409864669 0.04787234 0.07400709 20.1586 spindle)-like, microcephaly associated (Drosophila) 30016 Atrx: Alpha 120.99 183.34 102.72 558.59 325.41 576.41 338.6 384.09 383.86 0.317145573 0.048148148 0.06746914 23.1632 thalassemia/mental retardation syndrome X- linked homolog (human) 15284 AU040096: expressed 1327.17 938.18 1971.18 2586.3 2194.2 3019.8 2743.2 2441.9 2607.7 0.543384867 0.037914692 0.06336493 25.5363 sequence AU040096 8675 B230354K17Rik: RIKEN 814.67 430.9 611.56 2576.3 1355.6 1878.6 1425.7 1638.7 1475.3 0.358860153 0.025 0.05741667 43.3599 cDNA B230354K17 gene 15916 Bach1: BTB and CNC 214.4 51.49 267.98 509.03 500.69 370.86 552.06 427.69 703.89 0.348454093 0.038647343 0.06276973 25.7553 homology 1 8637 Bbs2: Bardet-Biedl 118.85 61.19 192.91 337.79 236.48 247.56 500.41 586.34 389.87 0.324523048 0.045602606 0.06908795 22.0603 syndrome 2 homolog (human) 8704 BC003965: cDNA 318.96 314.61 589.74 1242.2 913.8 906.78 1067.1 675.98 1003.8 0.421130361 0.044692737 0.06277462 26.9326 sequence BC003965 31179 BF642829: expressed 55.1 17.77 90.7 564.5 291.99 569.64 719.96 231.69 348.62 0.11998973 0 0.04888889 85.4286 sequence BF642829 1110 Bub3: budding uninhibited 163.69 146.39 195.19 499.57 444.31 468.08 309.06 361.39 554.54 0.383223042 0.046728972 0.07061267 21.6291 by benzimidazoles 3 homolog (S. cerevisiae) 18450 Bxdc1: brix domain 521.77 121.43 552.63 1496.2 1126.8 1048.1 945.53 776.39 1481.2 0.347916279 0.034482759 0.05551724 39.3557 containing 1 10968 C430004E15Rik: RIKEN 125.61 72.26 122.92 346.64 170.85 293.11 500.16 350.92 598.27 0.283891237 0.038277512 0.06291866 25.6253 cDNA C430004E15 gene 27736 C730049O14Rik: RIKEN 279.36 161.54 258.16 854.88 650.64 580.29 733.69 724.56 697.53 0.329621675 0.04 0.05737778 35.8955 cDNA C730049O14 gene 34773 Ccdc66: coiled-coil domain 152.66 109.96 220.57 681.69 370.27 538.09 732.89 447.88 631.69 0.284019738 0.036363636 0.05381818 40.4713 containing 66 29123 Cdca2: cell division cycle 209.02 187.77 269.92 719 518.46 652.95 696.51 623.21 617.99 0.348322414 0.032258065 0.06094086 30.5018 associated 2 41131 Cdca2: cell division cycle 160.58 179.33 233.01 408.1 505.8 456.62 590.37 765.51 518.81 0.353086549 0.042918455 0.06473534 24.6229 associated 2 8311 CDNA clone 1064.61 532.91 1115.12 1802.7 1683.2 1977.4 2026.2 1949.5 2208.4 0.465796823 0.031914894 0.05836879 33.0714 IMAGE: 30031514 4656 Cebpz: CCAAT/enhancer 801.7 466.96 1043.21 2020.2 1604.2 1858.7 1691.2 1501.9 1690.1 0.446033561 0.028571429 0.05825397 32.2117 binding protein zeta 15723 Cenpe: centromere protein E 595.49 593.11 496.28 1062.6 840.39 1209.8 1570.6 1201.9 1244.4 0.472642964 0.043290043 0.06494949 24.6295 39617 Ckap21: cytoskeleton 98.96 178.8 150.55 296.31 387.77 321.94 430.71 480.09 416.15 0.367180032 0.047761194 0.07039801 21.3319 associated protein 2-like 16339 Cndp2: CNDP dipeptidase 95.72 12.15 118.99 542.76 229.08 165.59 150.97 419.23 414.14 0.23609485 0.032786885 0.06057377 30.7138 2 (metallopeptidase M20 family) 13932 Cox17: cytochrome c 609.8 99.15 883.83 1560.4 816.01 1231.3 757.93 1492.8 1260 0.447513191 0.04494382 0.06275281 26.9721 oxidase, subunit XVII assembly protein homolog (yeast) 1878 Crlz1: charged amino acid 547.14 492.43 937.54 1867.1 1324.2 1689.6 1664.4 1073.1 1696.2 0.424524879 0.035714286 0.05494048 39.9162 rich leucine zipper 1 677 Ctsc: cathepsin C 560.59 170.75 535.58 1142.3 623.95 597.3 1072.2 767.24 1113.2 0.476631541 0.047619048 0.07378307 20.1335 10567 Cugbp1: CUG triplet 144.44 139.03 182.01 475.93 188.63 348.36 686.59 538.56 396.31 0.353388653 0.046822742 0.0693534 22.2407 repeat, RNA binding protein 1 10566 Cugbp1: CUG triplet 454.48 148.16 264.74 818.02 671.83 693.42 734.46 490.43 505.7 0.443235067 0.04719764 0.07229105 21.0766 repeat, RNA binding protein 1 41846 D14Abble: DNA segment, 166.7 221.03 266.86 493.13 316.45 653.17 637.61 639.35 503.72 0.40364059 0.047445255 0.06781022 22.983 Chr 14, Abbott 1 expressed 18143 D3Ertd300e: DNA 651.01 741.63 789.6 1222.2 863.98 1291 1855.7 1684.9 1719.9 0.505282071 0.042635659 0.06616279 23.6601 segment, Chr 3, ERATO Doi 300, expressed 38498 D530033C11Rik: RIKEN 890.62 74.97 669.69 1354.2 1034.7 1547.4 1172.7 959.68 1175.8 0.45145483 0.043650794 0.06470899 24.0102 cDNA D530033C11 gene 29413 Dcun1d3: DCN1, defective 112.69 125.06 198.24 483.09 350.59 483.79 304.94 421.64 437.94 0.35132293 0.044715447 0.06539295 24.0964 in cullin neddylation 1, domain containing 3 (S. cerevisiae) 15722 Ddx17: DEAD (Asp-Glu- 190.78 456.61 194.03 475.57 561.19 524.9 865.28 1016.7 851.49 0.391801878 0.04109589 0.06312024 25.2918 Ala-Asp) box polypeptide 17 16347 Ddx21: DEAD (Asp-Glu- 496.86 124.45 757.01 933.21 720.44 1161.8 1068.9 1079.2 1463.9 0.428886151 0.040462428 0.06244701 27.2505 Ala-Asp) box polypeptide 21 27562 Depdc1b: DEP domain 18.58 56.46 148.7 299.93 171.91 324.22 316.42 295.91 377.86 0.250513646 0.038461538 0.06087179 30.1319 containing 1B 14683 Dgke: diacylglycerol 343.02 114.18 420.65 1081.8 777.24 733.1 1097.9 905.2 997.74 0.313911367 0.03030303 0.0530303 46.7677 kinase, epsilon 7310 Dnajb11: DnaJ (Hsp40) 556.18 649.73 756.84 1341.8 1134.7 1077.5 1277.8 1479.7 1531.5 0.5005132 0.046511628 0.06949059 22.185 homolog, subfamily B, member 11 14950 Eif2c5: eukaryotic 73.43 7.99 58.25 207.56 115.15 151.62 314.47 175.57 291.88 0.222360199 0.046296296 0.07078189 21.539 translation initiation factor 2C, 5 22419 Eif3s6: eukaryotic 381.28 298.29 530.64 867.23 627.04 653.69 1252.5 944.86 908.52 0.460694538 0.047021944 0.07048067 21.6691 translation initiation factor 3, subunit 6 395 Eif3s7: eukaryotic 29.43 61.47 88.84 294.07 351.69 339.68 230.39 167.87 157.32 0.233274065 0.038961039 0.06056277 28.4566 translation initiation factor 3, subunit 7 (zeta) 153 Eif3s8: eukaryotic 647.41 374.43 471.72 1108.7 888.34 784.61 1267.7 1026.1 1313.4 0.467559382 0.048327138 0.06748451 23.1855 translation initiation factor 3, subunit 8 18771 EII2: elongation factor 298.51 184.57 392.63 1119.5 733.54 995.87 939.53 968.34 900.94 0.309562316 0.033333333 0.05511111 47.6055 RNA polymerase II 2 17713 Etnk1: Ethanolamine 159.03 73.22 93.44 636.72 598.27 683.95 479.48 375.04 558.65 0.195485743 0 0.03666667 65.0229 kinase 1 42522 Fancm: Fanconi anemia, 235.24 234.96 201.67 561.14 449.79 487.17 710.1 690.61 645.65 0.379109935 0.039215686 0.0625 25.9442 complementation group M 33019 Fancm: Fanconi anemia, 324.67 275.04 276.12 624.04 629.44 728.5 955.82 882.68 792.98 0.379684662 0.04137931 0.06165517 28.8393 complementation group M 16073 Fancm: Fanconi anemia, 372.48 232.77 365.4 583.78 592.92 710.05 789.6 732.26 922.82 0.448189166 0.048648649 0.07340541 20.3188 complementation group M 14660 Fen1: flap structure specific 461.57 282.56 398.88 1199.4 1125.7 829.3 821.82 831.08 814.02 0.406671055 0.049056604 0.0674717 23.3419 endonuclease 1 6438 Fv1: Friend virus 38.2 81.88 76.52 241.25 95.92 244.58 302.26 159.26 316.04 0.289264406 0.048991354 0.07193084 20.9108 susceptibility 1 18071 Fzd7: frizzled homolog 7 340.48 178.18 288.66 840.79 815.36 819.63 1126.2 951.13 832.39 0.299813573 0.023809524 0.05539683 43.1524 (Drosophila) 23587 Gapvd1: GTPase activating 129.82 259.4 193.47 424.38 502.98 467.39 685.61 645.29 353.59 0.378463517 0.048710602 0.07160458 20.8995 protein and VPS9 domains 1 22636 Gfpt1: glutamine fructose-6- 38.52 89.06 120.23 335.73 165.1 314.89 566.93 599.99 90.41 0.239077687 0.042328042 0.06405644 26.3748 phosphate transaminase 1 28204 Glb1: galactosidase, beta 1 1082.26 154.29 824.12 1713.4 1707.9 1919 2551.5 2521.8 2748 0.31313842 0 0.041 74.6783 33270 Gm104: gene model 104, 270.98 111.96 218.82 623.96 423.95 354.11 625.11 416.17 774.69 0.373997433 0.04676259 0.06773381 22.9284 (NCBI) 29375 Gm1564: gene model 1564, 200.31 157.46 220.69 547.93 543.11 730.67 543.28 424.1 561.78 0.345259589 0.041420118 0.06234714 27.4591 (NCBI) 3500 Gpatc4: G patch domain 440.58 205.69 292.42 950.82 529.03 789.31 962.71 725.77 902.34 0.386293771 0.034782609 0.05953623 31.3345 containing 4 9979 Gpatc4: G patch domain 1300.71 154.78 656.61 2341.4 1228.2 1953.3 2071.8 1558.3 1584.8 0.393399692 0.042553191 0.05496454 42.1856 containing 4 29821 Gtf3c1: general 1082.02 314.5 452.3 1080.6 901.53 1212.7 1452 1192.1 1707.2 0.490006758 0.049608355 0.07422106 20.0083 transcription factor III C 1 13878 Gtf3c4: general 249.77 12.55 161.14 474.48 220.1 217.44 516.42 384.03 566.54 0.355996822 0.045454545 0.06888528 22.0575 transcription factor IIIC, polypeptide 4 7302 Gtpbp4: GTP binding 505.74 834.95 1152 1902.8 1140.8 1610.7 1950.4 1522.4 1943.6 0.495037098 0.044025157 0.06255765 28.0427 protein 4 20122 H47: histocompatibility 47 624.17 411.69 853.39 1601.4 1273.8 1337.6 1610.6 1602.3 1546.1 0.421159518 0.03125 0.05572917 38.1717 16780 H47: histocompatibility 47 1553.67 678.07 1382.64 2610 1889.2 2344.4 2583.7 2481.4 2674.1 0.495709628 0.034482759 0.05862069 33.9839 14429 H47: histocompatibility 47 1937.91 764.71 1187.44 2611 1869.7 2265.5 2327.5 2522.8 2346.6 0.557987889 0.044217687 0.06821995 22.4819 29582 Hectd1: HECT domain 886.78 469.71 529.57 1198 860.21 1101.7 1757.5 1238.8 1402.2 0.499059992 0.049350649 0.07448485 19.9476 containing 1 8699 Hipk1: homeodomain 992.48 402.72 711.08 1281.1 954.65 1185.9 1575.7 1648.7 1861.9 0.495129872 0.045627376 0.06700887 23.4149 interacting protein kinase 1 8270 Igf2r: insulin-like growth 327.8 119.68 339.68 781.98 500.48 705.3 745.85 596 939.69 0.36875366 0.039370079 0.06091864 30.3013 factor 2 receptor 8271 Igf2r: insulin-like growth 169.96 242.38 158.23 528.54 492.61 528.94 459.73 649.21 498.88 0.361359253 0.046218487 0.06540616 24.4395 factor 2 receptor 22514 Ilf3: interleukin enhancer 170.07 35.32 121.1 560.62 295.08 376.34 300.48 289.94 360.17 0.299171183 0.046594982 0.06761051 22.9134 binding factor 3 7251 Incenp: inner centromere 393.46 237.19 218.41 663.52 579.94 476.28 892.65 816.19 920.58 0.390447811 0.042944785 0.06310838 27.6464 protein 21315 Ipo7: importin 7 1777.24 743.47 1888.27 2615.2 2038 2474.9 2454.8 2754.8 2633.6 0.588991329 0.048128342 0.07298574 20.2873 27085 Isg20l2: interferon 416.94 227.53 402 1147.7 772.85 990.8 770.46 676.05 841.48 0.402541876 0.044247788 0.06415929 24.9122 stimulated exonuclease gene 20-like 2 4798 Jmy: junction-mediating 165.05 95.76 208.4 547.49 231.34 463.45 532.88 603.44 674.49 0.30736729 0.036585366 0.05780488 34.7455 and regulatory protein 4799 Jmy: junction-mediating 886.39 251.37 566.34 1194 1060.9 1111.5 1676.9 1290.8 1588.2 0.43020715 0.04347826 0.06289855 27.7616 and regulatory protein 19905 Jmy: junction-mediating 187.78 141.18 219.35 543.3 293 427.2 657.56 428.2 656.69 0.36481402 0.04609929 0.06806147 22.8305 and regulatory protein 2694 Kctd9: potassium channel 171.19 85.46 175.44 439.95 379.75 353.67 485.57 295.15 503.25 0.351672947 0.044520548 0.0681621 22.5441 tetramerisation domain containing 9 20342 Kif11: kinesin family 351.66 218.63 237.15 802.55 400.74 666.11 896.31 538.17 967.58 0.37806277 0.035460993 0.06096927 29.2285 member 11 19155 Kif22: kinesin family 291.5 250.11 329.46 841.6 654.47 559 989.59 886.55 947.43 0.35709542 0.028985507 0.05560386 37.1006 member 22 7972 Kif22: kinesin family 202.55 190.1 260.35 873.55 734.19 599.86 722.03 806.28 1047.4 0.273030408 0.034482759 0.05172414 48.7204 member 22 15135 Kif2c: kinesin family 167.17 158.49 331.1 532.54 543.91 578.45 476.24 472.46 1022 0.362287382 0.047297297 0.06951577 22.3005 member 2C 21863 Klf9: Kruppel-like factor 9 1075.11 184.91 618.97 1413.6 1073.9 1024.2 1693.1 992.37 1695.4 0.476142088 0.046242775 0.07190751 20.9288 9017 L2hgdh: L-2- 356.73 197.34 475.3 1034.2 590.33 965.17 1621.2 1345.6 1417.6 0.295197523 0 0.03680556 58.3346 hydroxyglutarate dehydrogenase 12344 Larp1 /// LOC631268: La 347.33 50.62 240.65 510.75 581.65 447.49 684.6 681.6 1010.2 0.326124981 0.028037383 0.05772586 32.144 ribonucleoprotein domain family, member 1 /// similar to la related protein isoform 1 27871 Lemd3: LEM domain 355.22 46.19 248.38 639.18 502.36 726.84 660.72 542.9 577.78 0.356070777 0.044871795 0.06168803 28.2329 containing 3 21965 /// LOC546201 /// 1318.37 1146.56 2240.92 2919.6 2279.5 3009.7 2492.5 2865.6 3135.8 0.563483748 0.03960396 0.06283828 25.9718 LOC619753 /// LOC621019 /// LOC622792 /// LOC664993 /// LOC665003 /// LOC665558 /// LOC665616 /// LOC665711 /// LOC665718 /// LOC665723 /// LOC665802 /// LOC666058 /// LOC666140: similar to PRAME family member 8 /// expressed sequence AU018829 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar to PRAME family member 8 /// similar 10972 Ltv1: LTV1 homolog (S. cerevisiae) 174.72 230.6 499.42 754.54 608.63 673.92 720.95 681.5 835.41 0.423275126 0.046052632 0.069375 22.1069 27592 Mdc1: mediator of DNA 262.4 166.34 518.6 980.38 695.34 702.31 682.3 773.12 895.31 0.400671635 0.043478261 0.06484848 23.9741 damage checkpoint 1 20064 Mgat2: mannoside 469.73 304.14 823.62 1323.3 860.58 1140.1 1038.6 1107.9 1146.1 0.482879947 0.045138889 0.06842593 22.6204 acetylglucosaminyltransferase 2 19069 Mina: myc induced nuclear 78.98 36.19 157.22 515.36 223.46 260.41 415.61 176.74 570.73 0.251943523 0.035211268 0.06105634 29.1747 antigen 21512 Mkrn1: makorin, ring 648.36 512.8 1294.71 1919.8 1380 1377.3 1555.2 1824.2 2003.2 0.488259093 0.04519774 0.06293785 26.9961 finger protein, 1 6466 Mm.218588.1 254.43 33.9 245.82 906 787.64 785.29 730.81 656.42 846.69 0.226678125 0 0.04019608 65.2427 12365 Mm.29909.1 281.86 28.14 399.88 829.02 524.34 892.94 1101.1 1108.6 1025.5 0.25901034 0 0.03666667 63.2122 29718 Mnab: membrane 118.68 46.27 176.41 283.79 408.91 313.29 413.11 248.67 694.29 0.289035842 0.040909091 0.06340909 25.2435 associated DNA binding protein 8643 Mobk1b: MOB1, Mps One 331.14 291.72 770.54 1112.7 863.99 1204.8 1306.9 1049 1225.8 0.412053466 0.030612245 0.05911565 32.694 Binder kinase activator-like 1B (yeast) 7941 Mobk1b: MOB1, Mps One 254.91 242.34 466.56 736.04 605.17 626.58 639.84 1041.8 1058.4 0.409444571 0.047745358 0.07390805 20.1378 Binder kinase activator-like 1B (yeast) 791 Mrfap1: Morf4 family 768.71 852.78 1066.33 1873 1359.9 1748.1 1989.4 2140.2 2023.5 0.48280997 0.03539823 0.0600295 31.3818 associated protein 1 2811 Mtf2: metal response 1035.21 1134.68 1619.57 2148.1 1573.3 2029 2913.6 2368.9 2633.3 0.554570812 0.044303797 0.06973629 21.7746 element binding transcription factor 2 16360 Ndufc1: NADH 305.64 283.11 391.61 1442.1 822.36 1025.9 1048.3 788.41 1348.7 0.302783972 0.035714286 0.0497619 49.4498 dehydrogenase (ubiquinone) 1, subcomplex unknown, 1 14278 Nme1: expressed in non- 58.62 18.15 143.92 450.69 102.76 119.29 425.45 295.56 236.64 0.270720502 0.048387097 0.07321685 20.3045 metastatic cells 1, protein 23157 Osbpl7: oxysterol binding 208.36 123.05 167.34 291.45 385.78 284.54 615.7 485.5 504.16 0.38856622 0.048843188 0.07529563 19.8199 protein-like 7 10534 Oxnad1: oxidoreductase 230.13 169.82 311.6 693.65 782.99 681.59 465.88 438.48 324.58 0.42014425 0.047368421 0.0742193 20.0481 NAD-binding domain containing 1 10418 Pank3: pantothenate kinase 3 425.65 241.73 280.88 1151.2 770.81 1060.5 873.11 919.21 1010 0.327845955 0.024390244 0.05658537 43.2753 3006 Pdgfa: platelet derived 301.5 109.27 223.39 769.44 1041 424.85 654.37 303.32 583.26 0.335864925 0.03649635 0.06034063 29.6355 growth factor, alpha 12377 Pdrg1: p53 and DNA 372.77 252.95 540.97 715.57 694.98 822.93 1022.5 1047.5 1095.6 0.432177036 0.040201005 0.06324958 26.0102 damage regulated 1 12376 Pdrg1: p53 and DNA 285.31 282.96 545.59 789.75 643.57 739.91 846.21 866 924.2 0.463178117 0.048850575 0.0717433 20.9062 damage regulated 1 727 Pfkfb3: 6-phosphofructo-2- 39.57 6.24 92.23 213.6 178.27 137.99 367.86 210.92 349.81 0.189296856 0.040935673 0.06185185 27.429 kinase/fructose-2,6- biphosphatase 3 14762 Pgd: phosphogluconate 929.25 508.03 877.51 1851.3 1253.4 1745.2 1403.8 1529.3 1992.3 0.473598818 0.039473684 0.06089912 28.5711 dehydrogenase 15044 Pgd: phosphogluconate 864.91 479.01 841.06 1775 1198.1 1646 1302.6 1437.5 1852.4 0.474396469 0.042168675 0.06273092 27.5296 dehydrogenase 15538 Pgd: phosphogluconate 641.54 351.22 569.81 1194 750.15 1094.5 1037.2 1017.5 1353.6 0.48475081 0.046376812 0.07173913 20.9781 dehydrogenase 28991 Plcd4: phospholipase C, 85.67 50.61 173.34 335.85 224.94 209.08 437.46 324.88 403.75 0.319861981 0.045454545 0.06839161 22.7015 delta 4 16204 Ppgb: protective protein for 440.09 225.35 350.75 1117.8 569.65 1350.3 1365.1 642.54 1356.9 0.317445293 0 0.03811594 58.4023 beta-galactosidase 1352 Ppid /// Lamp3 /// 177.09 265.27 578.82 1140.3 699.01 928.31 1030.2 754.1 902.76 0.37442549 0.032608696 0.05804348 33.4589 LOC671770: peptidylprolyl isomerase D (cyclophilin D) /// lysosomal-associated membrane protein 3 /// similar to peptidylprolyl isomerase D 39148 Ppm1a: protein 678.05 348.48 381.66 1276.6 1065.7 1257 1597.5 1131.1 1120.3 0.378124375 0.027777778 0.05555556 36.5516 phosphatase 1A, magnesium dependent, alpha isoform 9696 Ppm1a: protein 132.05 88.38 124.3 565.15 304.18 544.53 369.01 388.93 396.41 0.268459355 0.033333333 0.06136111 30.7357 phosphatase 1A, magnesium dependent, alpha isoform 32940 Ppp1r3e: Protein 5.81 13.38 13.14 172.3 123.7 36.66 111.76 102.91 75.79 0.103768135 0.049723757 0.07308471 20.499 phosphatase 1, regulatory (inhibitor) subunit 3E 15897 Pramel7: preferentially 228.49 144.58 867.63 970.28 608.23 1186 963.95 982.9 977.84 0.436162808 0.038095238 0.06279365 25.6083 expressed antigen in melanoma like 7 15898 Pramel7: preferentially 883.77 273.04 670.2 1610.9 1098.7 1406.8 1266 1347.1 1586.8 0.439380494 0.03875969 0.06098191 30.2002 expressed antigen in melanoma like 7 7006 Prkcd: protein kinase C, 235.8 93.35 81.71 712.82 315.54 733.67 910.26 661.36 733.23 0.202051696 0 0.03909091 73.8504 delta 9218 Prmt6: protein arginine N- 738.14 448.83 800.51 1347.3 1072.8 1130.9 1415.4 1423.3 1354.9 0.513255025 0.044827586 0.06847126 22.56 methyltransferase 6 41444 Prpf19: PRP19/PSO4 pre- 3993.02 2736.93 2277.87 4887.6 4659.6 4958.5 4053.2 4990.6 4177.1 0.64976133 0.04664723 0.07188533 21.0008 mRNA processing factor 19 homolog (S. cerevisiae) 33047 Prr11: proline rich 11 401.64 173.26 234.39 568.15 688.18 606.56 817.5 1134 740.86 0.355318761 0.036231884 0.06014493 29.5659 35103 Prr11: proline rich 11 265.25 149.08 442.11 729.69 571.34 733.59 873.03 564.31 1014.1 0.381823653 0.040697674 0.06170543 27.3805 21158 Psat1: phosphoserine 608.23 383.49 505.63 1268.1 1111.2 1110.2 1163.3 1113 1052.3 0.439232447 0.043010753 0.06390681 26.5312 aminotransferase 1 14945 Psma6: proteasome 297.18 193.17 579.11 823.99 814.83 842.51 1149.9 1450.2 1653.8 0.31757146 0.039215686 0.05627451 41.0024 (prosome, macropain) subunit, alpha type 6 14001 Ptdss2: phosphatidylserine 286.3 79.67 434.04 847.59 360.31 528.7 764.33 553.32 801.99 0.414917121 0.045901639 0.06926776 22.0925 synthase 2 3935 Purb: purine rich element 255.68 124.63 215.26 618.23 457.69 488.12 438.8 529.05 494.18 0.393626056 0.04851752 0.07339623 20.3063 binding protein B 16286 Rab1: RAB1, member RAS 24.78 29.32 63.21 200.41 213.31 158.37 260.27 168.49 186.44 0.197609683 0.037735849 0.06314465 25.5279 oncogene family 15338 Rab20: RAB20, member 448.47 171.13 416.25 593.19 602.78 611.39 1207 970.25 1217.6 0.398230769 0.045977011 0.06689655 23.5179 RAS oncogene family 4228 Rbm35b: RNA binding 187.48 63.54 221.76 590.29 628.16 453.65 363.16 321 412.3 0.34153495 0.047619048 0.06794872 22.9952 motif protein 35b 12058 Rnf6: ring finger protein 508.38 239.28 418.61 655.12 583.25 868.77 1096.2 908.12 1006.9 0.455713959 0.047794118 0.06800245 23.0191 (C3H2C3 type) 6 12057 Rnf6: ring finger protein 861.12 396.56 614.69 1246.8 778.27 939.73 1510 1251.2 1413.2 0.524537304 0.049095607 0.07514212 19.8721 (C3H2C3 type) 6 1293 Rrs1: RRS1 ribosome 618.8 397.87 439.42 1053.2 649.43 1070.2 1408.1 1440.1 939.09 0.443918374 0.042372881 0.06426554 24.5877 biogenesis regulator homolog (S. cerevisiae) 8403 Rwdd4a: RWD domain 120.1 127.06 198.13 517.17 347.78 401.78 607.87 348.3 679.49 0.30684367 0.04109589 0.06171233 28.8054 containing 4A 20481 Sdad1: SDA1 domain 850.27 363.33 872.76 2204.8 1724.2 2050.9 2051.9 2375.7 1968.4 0.337163067 0 0.03539683 62.6786 containing 1 15545 Sf3b2: splicing factor 3b, 805.59 473.95 826.78 1604.5 2014.8 1868.8 1091.8 1101.2 1830 0.442914549 0.028169014 0.05497653 36.8781 subunit 2 12258 Sfrs1: splicing factor, 1313.28 772.48 1279.84 2058.8 1861 1951.5 1990.7 2140.9 2193.1 0.551915042 0.048780488 0.07106707 21.4237 arginine/serine-rich 1 (ASF/SF2) 4980 Sgpp1: sphingosine-1- 171.97 94.46 279.34 1215.3 589.36 577.14 509.63 536.21 763.86 0.260417512 0.032258065 0.05677419 38.3871 phosphate phosphatase 1 4981 Sgpp1: sphingosine-1- 1314.88 188.41 379.99 1556.5 1386.4 1522.7 1138.2 1603.8 1205.4 0.447708184 0.033613445 0.06098039 30.8513 phosphate phosphatase 1 18042 Sgpp1: sphingosine-1- 31.01 17.03 39.22 176.04 188.98 215.43 109.27 132.56 153.26 0.178895791 0.044354839 0.06548387 24.0389 phosphate phosphatase 1 1917 Slc12a2: solute carrier 437.13 331.4 303.71 1012.6 574.08 711.55 831.2 898.12 1082.7 0.419649444 0.041450777 0.06310881 26.2992 family 12, member 2 16856 Slc12a2: solute carrier 153.39 179.89 175.06 527.45 337.21 487.48 447.9 572.27 515.56 0.352051858 0.043715847 0.06347905 26.6694 family 12, member 2 21716 Slc1a4: solute carrier 60.95 35.65 114.42 292.45 192.95 238.64 177.44 338.73 362.16 0.263384861 0.043668122 0.06537118 24.6402 family 1 (glutamate/neutral amino acid transporter), member 4 28457 Slc30a1: solute carrier 317.74 103.14 73.18 315.4 343.75 619.79 393.91 491.5 503.8 0.370338999 0.047619048 0.07036706 21.3192 family 30 (zinc transporter), member 1 23716 Sltm: SAFB-like, 370.13 284.47 502.78 1011.1 760.09 1052 1179.5 795.6 946.04 0.402964314 0.034188034 0.06111111 30.8935 transcription modulator 7575 Smarcc1: SWI/SNF related, 97.38 219.78 155.82 345.56 264.16 208.33 557.93 543.22 522.86 0.38736149 0.049222798 0.0747323 19.9146 matrix associated, actin dependent regulator of chromatin, subfamily c, member 1 6834 Smarce1: SWI/SNF related, 873.62 915.47 718.44 1533.2 1416.9 1757.6 1787.9 1926.5 1710.1 0.49496406 0.041666667 0.06248016 27.4725 matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 6044 Sos1: Son of sevenless 134.91 61.07 109.98 438.22 273.17 373.78 444.95 294.97 346.44 0.281792101 0.039735099 0.06119205 28.5896 homolog 1 (Drosophila) 6045 Sos1: Son of sevenless 391.93 223.27 270.95 684.56 368.73 779.87 937.33 493.55 698.66 0.447245565 0.048913043 0.07344203 20.356 homolog 1 (Drosophila) 27178 Spata2: spermatogenesis 1669.65 719.38 963.1 2142.9 1761.6 1953.7 1664.5 2350.8 2119.4 0.559020019 0.047477745 0.07050445 21.2734 associated 2 15690 Spint2: serine protease 120.15 171.41 256.46 612.14 318.08 490.9 552.94 367.02 613.78 0.370927895 0.041284404 0.06328746 25.2973 inhibitor, Kunitz type 2 21622 Stt3a: STT3, subunit of the 295.43 563.39 363.82 1099.3 829.32 1154.4 987.79 752.3 707.18 0.442161261 0.045801527 0.06703562 23.437 oligosaccharyltransferase complex, homolog A (S. cerevisiae) 6577 suppressor of Ty 4 homolog 782.52 691.08 832.99 1708.4 1408.4 1683.3 1689.4 2017.7 2324.6 0.425897785 0.034090909 0.0580303 33.971 1 (S. cerevisiae) /// suppressor of Ty 4 homolog 2 (S. cerevisiae) 1745 Tacc3: transforming, acidic 738.85 414.57 618.79 1661.2 1187.9 1268.8 1516.9 1282.6 1702 0.411215669 0.035294118 0.05729412 34.3614 coiled-coil containing protein 3 13841 Tbl2: transducin (beta)-like 2 293.54 36.54 247.36 684.47 780.75 476.82 685.89 393.26 569.1 0.321667609 0.0375 0.057375 35.1428 41362 Terf2ip: telomeric repeat 127.85 108.83 96.14 286.88 330.88 351.36 345.81 519.43 330.16 0.307523146 0.04797048 0.06747847 23.1137 binding factor 2, interacting protein 182 Tfg: Trk-fused gene 388.74 156.37 629.82 928.5 564.98 679.38 871.81 1022.6 1079 0.456614208 0.046428571 0.0677619 22.8893 7468 Tgoln1: trans-golgi network 305.53 236.42 345.51 671.72 450.68 487.94 700.65 843.07 702.27 0.46026144 0.047493404 0.0739314 20.0806 protein 3061 Timd2: T-cell 608.39 151.76 231.44 1866.9 1351.1 1401.1 1475.4 1242.5 1993.4 0.212552423 0 0.06166667 97.4881 immunoglobulin and mucin domain containing 2 1794 Timm10: translocase of 207.76 55.6 617.54 1237.7 550.92 497.86 560.37 1173.8 1446.2 0.322267911 0.038961039 0.05835498 35.3576 inner mitochondrial membrane 10 homolog (yeast) 785 Tmed6: transmembrane 254.44 20.44 279.48 508.83 418.62 577.06 745.64 731.85 729.56 0.298720754 0.037037037 0.05450617 40.4979 emp24 protein transport domain containing 6 23223 Tmpo: thymopoietin 372.55 239.05 785 1127.4 1035.5 974.18 1028.2 951.54 1084.8 0.450399171 0.042735043 0.06450142 24.6087 13926 Tomm22: translocase of 1013.62 632.86 904.75 2273.2 1748.6 1962.2 1195.2 1371.2 1705.4 0.497524304 0.040609137 0.06323181 26.1029 outer mitochondrial membrane 22 homolog (yeast) 16924 Tor1b: torsin family 1, 272.73 156.58 572.98 1028.7 649.17 887.96 740.56 964.62 1195.4 0.36670801 0.037974684 0.05776371 35.2 member B 21932 Transcribed locus 332.77 106.56 140.03 583.75 309.89 572.13 653.87 636.22 766.49 0.328962199 0.032258065 0.0578853 33.3722 43944 Transcribed locus 53.89 21.65 39.31 224.22 170.32 140.35 49.01 235.17 219.21 0.221231267 0.046153846 0.06666667 23.5864 24471 Tsc22d2: TSC22 domain 936.98 613.69 879.83 1530.6 1318.9 1453.7 2101.3 2010.4 1899.3 0.47129429 0.035971223 0.06131894 29.3405 family 2 10769 Ttf1: transcription 42.37 81.67 164.99 294.59 226.16 368.82 336.41 367.68 251.53 0.313279391 0.045936396 0.06791519 22.8092 termination factor 1 14944 Txndc1: thioredoxin 424.55 133.69 462.39 960.94 645.2 984.25 612.43 1057.4 631.05 0.417324638 0.045454545 0.06567493 24.2087 domain containing 1 22950 Unkl: unkempt-like 270.84 139.44 154.65 747.39 286.66 573.67 677.07 831.48 565.56 0.306874571 0.028571429 0.05490476 37.0961 (Drosophila) 16306 Usp10: ubiquitin specific 173.21 255.12 344.42 838.32 498.36 592.08 738.05 449.15 994.08 0.376030404 0.041025641 0.06345299 26.1651 peptidase 10 12733 Utp11l: UTP11-like, U3 955.84 514.61 1811.24 2092.8 2024.9 1852.2 1938.2 1738.6 2374.9 0.545964687 0.046920821 0.07209189 21.0368 small nucleolar ribonucleoprotein, (yeast) 27185 Utp15: UTP15, U3 small 222.46 131.63 302.63 1588.6 802.68 700.69 623.36 1475.8 537.97 0.22925845 0.037037037 0.0491358 50.5511 nucleolar ribonucleoprotein, homolog (yeast) 15510 Wbscr1: Williams-Beuren 117.48 136.2 356.85 655.34 402.2 299.57 683.74 452.6 930.59 0.356613825 0.046025105 0.06517434 24.4325 syndrome chromosome region 1 homolog (human) 26959 Wdr3: WD repeat domain 3 772.19 388.92 483.21 1122.9 1121.4 1247.2 1065.7 962.84 1081.4 0.498168587 0.049046322 0.07336966 20.3716 21792 Zfp444: Zinc finger protein 75.01 31.45 145.74 452.64 198.57 309.81 294.53 537.31 689.29 0.203210926 0.041666667 0.055 41.8997 444 39491 Zfp710: zinc finger protein 371.26 333.7 313.27 900.66 784.47 1074.7 975.36 1333.3 979.43 0.336722951 0.037735849 0.05540881 40.5004 710

indicates data missing or illegible when filed 

1. A method of evaluating a female subject for an in vitro fertilization procedure, comprising: obtaining items of information from a female subject to provide a profile for said female subject, wherein each item of information relate to preselected patient variables; comparing said profile for said female subject to a library of known profile patterns known to be indicative of responsiveness to an in vitro fertilization procedure using an algorithm based upon said preselected patient variables, wherein said comparing provides an evaluation of said female subject for an in vitro fertilization procedure.
 2. The method of claim 1, wherein said in vitro fertilization procedure is at least a second vitro fertilization procedure for said female subject.
 3. The method of claim 1, wherein said in vitro fertilization procedure comprises determining a number of embryos for implantation.
 4. The method of claim 1, wherein said in vitro fertilization procedure provides for a live birth event.
 5. The method of claim 1, wherein said female subject is a pre-in vitro fertilization (pre-IVF) procedure patient.
 6. The method of claim 5, wherein said preselected patient variables comprises age, diminished ovarian reserve, 3 follicle stimulating hormone (FSH) level, body mass index, polycystic ovarian disease, season, unexplained female infertility, number of spontaneous miscarriages, year, other causes of female infertility, number of previous pregnancies, number of previous term deliveries, endometriosis, tubal disease, tubal ligation, male infertility, uterine fibroids, hydrosalpinx, or male infertility causes.
 7. The method of claim 1, wherein said female subject is a pre-surgical (pre-OR) procedure patient.
 8. The method of claim 7, wherein said preselected patient variables comprises age, endometrial thickness, total number of oocytes, total amount of gonatropins administered, number of total motile sperm after wash, number of total motile sperm before wash, day 3 follicle stimulating hormone (FSH) level, body mass index, sperm collection, age of spouse, season number of spontaneous miscarriages, unexplained female infertility, number of previous term deliveries, year, number of previous pregnancies, other causes of female infertility, endometriosis, male infertility, tubal ligation, polycystic ovarian disease, tubal disease, sperm from donor, hydrosalpinx, uterine fibroids, or male infertility causes.
 9. The method of claim 1, wherein said female subject is a post-in vitro fertilization (post-IVF) procedure patient.
 10. The method of claim 9, wherein said preselected patient variables comprises blastocyst development rate, total number of embryos, total amount of gonatropins administered, endometrial thickness, flare protocol, average number of cells per embryo, type of catheter used, percentage of 8-cell embryos transferred, day 3 follicle stimulating hormone (FSH) level, body mass index, number of motile sperm before wash, number of motile sperm after wash, average grade of embryos, day of embryo transfer, season, number of spontaneous miscarriages, number of previous term deliveries, oral contraceptive pills, sperm collection, percent of unfertilized eggs, number of embryos arrested at 4-cell stage, compaction on day 3 after transfer, percent of normal fertilization, percent of abnormally fertilized eggs, percent of normal and mature oocytes, number of previous pregnancies, year, polycystic ovarian disease, unexplained female infertility, tubal disease, male infertility only, male infertility causes, endometriosis, other causes of female infertility, uterine fibroids, tubal ligation, sperm from donor, hydrosalpinx, performance of ICSI, or assisted hatching.
 11. The method of claim 1, wherein said method comprises obtaining items of information relating to at least two preselected patient variables.
 12. The method of claim 1, wherein said method comprises obtaining items of information relating to at least five preselected patient variables.
 13. The method of claim 12, wherein preselected patient variables is given a weighted relative importance in relation to other preselected patient variables.
 14. The method of claim 1, wherein said preselected patient variables comprises age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, number of 8-cell embryos transferred.
 15. The method of claim 1, further comprising determining an expression level of one or more infertility indicator genes and comparing said expression level to a control gene expression profile known to be indicative of responsiveness to an in vitro fertilization procedure.
 16. The method of claim 15, wherein said infertility indicator genes comprise Oct4, Eif3c, Papola, Piwil2, Eif3b, Eif4b, Rbm3, and Cpsf4.
 17. The method of claim 15, wherein said expression level of one or more infertility indicator genes is done by using a BioMark® Dynamic Array, RT-PCR, or whole whole-transcriptome sequencing.
 18. The method of claim 15, wherein said expression level of one or more infertility indicator genes is determined for an embryo.
 19. The method of claim 18, wherein said embryo is in arrested development following fertilization.
 20. The method of claim 15, wherein said expression level of one or more infertility indicator genes is determined for an oocyte.
 21. The method of claim 20, wherein said oocyte is in arrested development following fertilization.
 22. The method of claim 1, wherein said comparing said profile for said female subject comprises applying a decision rule.
 23. The method of claim 1, wherein said data analysis algorithm comprises use of a classification tree.
 24. The method of claim 1, wherein said data analysis algorithm is nonparametric.
 25. The method of claim 24, wherein said data analysis algorithm detects differences in a distribution of feature values.
 26. The method of claim 25, wherein said nonparametric algorithm comprises using a Wilcoxon Signed Rank Test.
 27. The method of claim 1, wherein said data analysis algorithm comprises using a multiple additive regression tree or by gradient boosted machine (GBM).
 28. The method of claim 1, wherein said data analysis algorithm is a logistic regression.
 29. A method of evaluating a female subject for an in vitro fertilization procedure, comprising: obtaining items of information from a female subject to provide a profile for said female subject, wherein each item of information relate to preselected patient variables; determining an expression level of one or more infertility indicator genes; comparing said profile for said female subject to a library of known profile patterns known to be indicative of responsiveness to an in vitro fertilization procedure using an algorithm based upon said preselected patient variables; and comparing said expression level of said one or more infertility indicator genes to a control gene expression profile known to be indicative of responsiveness to an in vitro fertilization procedure wherein said comparing said profile for said female subject and said expression level of said one or more infertility indicator genes provides an evaluation of said female subject for an in vitro fertilization procedure.
 30. The method of claim 29, wherein said in vitro fertilization procedure is at least a second vitro fertilization procedure for said female subject.
 31. The method of claim 29, wherein said in vitro fertilization procedure comprises a determining a number of embryos for implantation.
 32. The method of claim 29, wherein said in vitro fertilization procedure provides for a live birth event.
 33. The method of claim 29, wherein said in vitro fertilization procedure provides for a live birth event.
 34. The method of claim 29, wherein said female subject is a pre-in vitro fertilization (pre-IVF) procedure patient.
 35. The method of claim 34, wherein said preselected patient variables comprises age, diminished ovarian reserve, 3 follicle stimulating hormone (FSH) level, body mass index, polycystic ovarian disease, season, unexplained female infertility, number of spontaneous miscarriages, year, other causes of female infertility, number of previous pregnancies, number of previous term deliveries, endometriosis, tubal disease, tubal ligation, male infertility, uterine fibroids, hydrosalpinx, or male infertility causes.
 36. The method of claim 29, wherein said female subject is a pre-surgical (pre-OR) procedure patient.
 37. The method of claim 36, wherein said preselected patient variables comprises age, endometrial thickness, total number of oocytes, total amount of gonatropins administered, number of total motile sperm after wash, number of total motile sperm before wash, day 3 follicle stimulating hormone (FSH) level, body mass index, sperm collection, age of spouse, season number of spontaneous miscarriages, unexplained female infertility, number of previous term deliveries, year, number of previous pregnancies, other causes of female infertility, endometriosis, male infertility, tubal ligation, polycystic ovarian disease, tubal disease, sperm from donor, hydrosalpinx, uterine fibroids, or male infertility causes.
 38. The method of claim 29, wherein said female subject is a post-in vitro fertilization (post-IVF) procedure patient.
 39. The method of claim 38, wherein said preselected patient variables comprises blastocyst development rate, total number of embryos, total amount of gonatropins administered, endometrial thickness, flare protocol, average number of cells per embryo, type of catheter used, percentage of 8-cell embryos transferred, day 3 follicle stimulating hormone (FSH) level, body mass index, number of motile sperm before wash, number of motile sperm after wash, average grade of embryos, day of embryo transfer, season, number of spontaneous miscarriages, number of previous term deliveries, oral contraceptive pills, sperm collection, percent of unfertilized eggs, number of embryos arrested at 4-cell stage, compaction on day 3 after transfer, percent of normal fertilization, percent of abnormally fertilized eggs, percent of normal and mature oocytes, number of previous pregnancies, year, polycystic ovarian disease, unexplained female infertility, tubal disease, male infertility only, male infertility causes, endometriosis, other causes of female infertility, uterine fibroids, tubal ligation, sperm from donor, hydrosalpinx, performance of ICSI, or assisted hatching.
 40. The method of claim 29, wherein said method comprises obtaining items of information relating to at least two preselected patient variables.
 41. The method of claim 29, wherein said method comprises obtaining items of information relating to at least five preselected patient variables.
 42. The method of claim 41, wherein preselected patient variables is given a weighted relative importance in relation to other preselected patient variables.
 43. The method of claim 29, wherein said preselected patient variables comprises age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, and number of 8-cell embryos transferred.
 44. The method of claim 29, wherein said infertility indicator genes comprise Oct4, Eif3c, Papola, Piwil2, Eif3b, Eif4b, Rbm3, and Cpsf4.
 45. The method of claim 29, wherein said expression level of one or more infertility indicator genes is done by using a BioMark® Dynamic Array, RT-PCR, or whole whole-transcriptome sequencing.
 46. The method of claim 29, wherein said expression level of one or more infertility indicator genes is determined for an embryo.
 47. The method of claim 46, wherein said embryo is in arrested development following fertilization.
 48. The method of claim 29, wherein said expression level of one or more infertility indicator genes is determined for an oocyte.
 49. The method of claim 48, wherein said embryo is in arrested development following fertilization.
 50. The method of claim 29, wherein said comparing said profile for said female subject comprises applying a decision rule.
 51. The method of claim 29, wherein said data analysis algorithm comprises use of a classification tree.
 52. The method of claim 29, wherein said data analysis algorithm is nonparametric.
 53. The method of claim 52, wherein said data analysis algorithm detects differences in a distribution of feature values.
 54. The method of claim 52, wherein said nonparametric algorithm comprises using a Wilcoxon Signed Rank Test.
 55. The method of claim 29, wherein said data analysis algorithm comprises using a multiple additive regression tree or by gradient boosted machine (GBM).
 56. The method of claim 29, wherein said data analysis algorithm is a logistic regression.
 57. A system for analysis of data in evaluating a female subject for an in vitro fertilization procedure, comprising: a computing environment; an input device, connected to the computing environment, to receive data from a user, wherein the data received comprises items of information from a female subject to provide a profile for said female subject, wherein each item of information relate to preselected patient variables, an output device, connected to the computing environment, to provide information to the user; and a computer readable storage medium having stored thereon at least one algorithm to provide for comparing the profile for the female subject to a library of known profile patterns known to be indicative of responsiveness to an in vitro fertilization procedure, wherein the system provides results that can be used for generation of a report providing an analysis of data in evaluating a female subject for an in vitro fertilization procedure.
 58. The system of claim 57, wherein the computing environment comprises a local computer local to the user and a remote computer at a site remote to the user, wherein the local computer and the remote computer are connected through a network, and wherein the computer readable storage medium is provided on the remote computer.
 59. The system of claim 57, wherein said input device is a personal computing device or a Smartphone device.
 60. The system of claim 57, wherein said connection of the input device to the computing device is via a wired connection or a wireless connection.
 61. The system of claim 57, wherein said wireless connection is via a wireless LAN connection, Bluetooth connection protocol, ZigBee connection protocol, radio-frequency connection protocol, or a cellular phone connection protocol.
 62. The system of claim 61, wherein said cellular phone connection is via code derived multiple access (CDMA) or via a global system for mobile communication (GSM).
 63. The system of claim 57, wherein said in vitro fertilization procedure is at least a second vitro fertilization procedure for said female subject.
 64. The system of claim 57, wherein said in vitro fertilization procedure comprises a determining a number of embryos for implantation.
 65. The system of claim 57, wherein said in vitro fertilization procedure provides for a live birth event.
 66. The system of claim 57, wherein said in vitro fertilization procedure provides for a live birth event.
 67. The system of claim 57, wherein said female subject is a pre-in vitro fertilization (pre-IVF) procedure patient.
 68. The system of claim 57, wherein said preselected patient variables comprises age, diminished ovarian reserve, 3 follicle stimulating hormone (FSH) level, body mass index, polycystic ovarian disease, season, unexplained female infertility, number of spontaneous miscarriages, year, other causes of female infertility, number of previous pregnancies, number of previous term deliveries, endometriosis, tubal disease, tubal ligation, male infertility, uterine fibroids, hydrosalpinx, or male infertility causes.
 69. The system of claim 57, wherein said female subject is a pre-surgical (pre-OR) procedure patient.
 70. The system of claim 69, wherein said preselected patient variables comprises age, endometrial thickness, total number of oocytes, total amount of gonatropins administered, number of total motile sperm after wash, number of total motile sperm before wash, day 3 follicle stimulating hormone (FSH) level, body mass index, sperm collection, age of spouse, season number of spontaneous miscarriages, unexplained female infertility, number of previous term deliveries, year, number of previous pregnancies, other causes of female infertility, endometriosis, male infertility, tubal ligation, polycystic ovarian disease, tubal disease, sperm from donor, hydrosalpinx, uterine fibroids, or male infertility causes.
 71. The system of claim 57, wherein said female subject is a post-in vitro fertilization (post-IVF) procedure patient.
 72. The system of claim 71, wherein said preselected patient variables comprises blastocyst development rate, total number of embryos, total amount of gonatropins administered, endometrial thickness, flare protocol, average number of cells per embryo, type of catheter used, percentage of 8-cell embryos transferred, day 3 follicle stimulating hormone (FSH) level, body mass index, number of motile sperm before wash, number of motile sperm after wash, average grade of embryos, day of embryo transfer, season, number of spontaneous miscarriages, number of previous term deliveries, oral contraceptive pills, sperm collection, percent of unfertilized eggs, number of embryos arrested at 4-cell stage, compaction on day 3 after transfer, percent of normal fertilization, percent of abnormally fertilized eggs, percent of normal and mature oocytes, number of previous pregnancies, year, polycystic ovarian disease, unexplained female infertility, tubal disease, male infertility only, male infertility causes, endometriosis, other causes of female infertility, uterine fibroids, tubal ligation, sperm from donor, hydrosalpinx, performance of ICSI, or assisted hatching.
 73. The system of claim 57, wherein said method comprises obtaining items of information relating to at least two preselected patient variables.
 74. The system of claim 57, wherein said method comprises obtaining items of information relating to at least five preselected patient variables.
 75. The system of claim 74, wherein preselected patient variables is given a weighted relative importance in relation to other preselected patient variables.
 76. The system of claim 57, wherein said preselected patient variables comprises age, total number of embryos, rate of cleavage arrest, number of 8-cell embryos, day 3 follicle stimulating hormone (FSH) level, and number of 8-cell embryos transferred.
 77. The system of claim 57, wherein the data received further comprises an expression level of one or more infertility indicator genes.
 78. The system of claim 77, wherein said infertility indicator genes comprise Oct4, Eif3c, Papola, Piwil2, Eif3b, Eif4b, Rbm3, and Cpsf4.
 79. The system of claim 77, wherein said expression level of one or more infertility indicator genes is done by using a BioMark® Dynamic Array, RT-PCR, or whole whole-transcriptome sequencing.
 80. The system of claim 77, wherein said expression level of one or more infertility indicator genes is determined for an embryo.
 81. The system of claim 80, wherein said embryo is in arrested development following fertilization.
 82. The system of claim 77, wherein said expression level of one or more infertility indicator genes is determined for an oocyte.
 83. The system of claim 82, wherein said embryo is in arrested development following fertilization.
 84. The system of claim 57, wherein said comparing comprises applying a decision rule.
 85. The system of claim 57, wherein said data analysis algorithm comprises use of a classification tree.
 86. The system of claim 57, wherein said data analysis algorithm is nonparametric.
 87. The system of claim 86, wherein said data analysis algorithm detects differences in a distribution of feature values.
 88. The system of claim 86, wherein said nonparametric algorithm comprises using a Wilcoxon Signed Rank Test.
 89. The system of claim 57, wherein said data analysis algorithm comprises using a multiple additive regression tree or by gradient boosted machine (GBM).
 90. The system of claim 57, wherein said data analysis algorithm is a logistic regression. 